{"id":156295,"date":"2014-08-23T14:27:06","date_gmt":"2014-08-23T17:27:06","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=156295"},"modified":"2017-10-20T14:24:27","modified_gmt":"2017-10-20T16:24:27","slug":"vanderlan-da-silva-bolzani-chemistry-natural-products","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/vanderlan-da-silva-bolzani-chemistry-natural-products\/","title":{"rendered":"Vanderlan da Silva Bolzani: The chemistry of natural products"},"content":{"rendered":"

\"\"L\u00e9o Ramos<\/span>It was the desire to become a researcher and study chemistry oriented towards understanding nature that led Vanderlan da Silva Bolzani to leave her parents’ home in Jo\u00e3o Pessoa, in the state of Para\u00edba, in the mid-1970s to work on her master’s degree in S\u00e3o Paulo. “I arrived with nothing but courage,” recalls Bolzani, who later would become a professor at the Institute of Chemistry, S\u00e3o Paulo State University (Unesp) Araraquara and an internationally recognized researcher for her work in the field of the chemistry of natural products. “At the time, I was not working and, in order to support a daughter in S\u00e3o Paulo, the family needed money. My family had a meeting and my father said that he would make great sacrifices to support me during the first few months, but after that I needed to find a way to support myself,” recalls the researcher.<\/p>\n

Bolzani obtained her bachelor’s degree in Pharmacy from the Federal University of Para\u00edba, where she had originally started as a medical student. Her mother was of Portuguese decent, while her father’s family was indigenous. She attributes her interest in the chemistry of nature to her paternal genetic heritage. It was further strengthened during her undergraduate studies by teachers who awakened her passion for the field of chemistry that comes closest to biology.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n
Age:<\/strong><\/td>\n<\/tr>\n
64<\/td>\n<\/tr>\n
Specialty:<\/strong><\/td>\n<\/tr>\n
Chemistry of natural products<\/td>\n<\/tr>\n
Education:<\/strong><\/td>\n<\/tr>\n
Federal University of Para\u00edba (UFPB), undergraduate (1972); University of S\u00e3o Paulo (USP), master’s (1978) and PhD (1982); Virginia Polytechnic Institute and State University, post-doctorate research (1992-1994)<\/td>\n<\/tr>\n
Institution:<\/strong><\/td>\n<\/tr>\n
Institute of Chemistry, S\u00e3o Paulo State University (Unesp), Araraquara<\/td>\n<\/tr>\n
Scientific production:<\/strong><\/td>\n<\/tr>\n
198 scientific articles, cited 2,377 times. Supervised 19 master’s theses and 20 PhD dissertations. Supervised 20 post-doctorate researchers<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

But when she arrived in S\u00e3o Paulo, she suffered some setbacks. The researcher who had agreed to be her advisor, Paulo de Carvalho, died of a massive heart attack and her roommate had an epileptic seizure. Her family’s support helped her get through that difficult period and later when, while working on her PhD, with two small children, her husband, the sociologist Jorge Bolzani, suffered a stroke at the age of 38 that prevented him from working for the rest of his life\u2014he died in 2011 at the age of 60.<\/span><\/p>\n

This and other adversities did not discourage this “timid girl from the poor Northeast” who, supervised by her great mentor, the chemist Otto Gottlieb, one of the pioneers in the chemistry of natural products in Brazil, achieved national and international recognition, including receiving the Distinguished Women in Science Award from the American Chemical Society (ACS) and the International Union of Pure and Applied Chemistry (IUPAC) in 2011.<\/span><\/p>\n

In addition to her dual role as mother (and today, grandmother) and researcher, Bolzani was strongly involved in academic politics, seeking to broaden international cooperation between scientific fields and reduce the glass ceiling that bars women from holding administrative positions in academia. She was president of the Brazilian Chemical Society (SBQ) from 2008 to 2010 and is deputy director of the Unesp Innovation Agency, where she coordinates a group of researchers that has investigated approximately 170 plant extracts and isolated 640 substances, some with pharmacological potential.<\/span><\/p>\n

Below are the highlights of an interview with Bolzani.<\/span><\/p>\n

What is the most significant award you’ve received?
\n<\/span><\/strong>The Distinguished Women in Science Award, an international competition among women from all continents. Some were chosen from each continent. They were nominated by scientific societies and researchers. I was nominated by Professor Adriano Andicopulo and Alejandra Palermo, of the Royal Society of Chemistry, and other foreign colleagues, including Gerard Bringmann, of the University of W\u00fcrzburg, Germany, and Leslie Gunatilaka, of the University of Arizona, in the field of natural products.<\/span><\/p>\n

When was this?
\n<\/span><\/strong>In 2011, the International Year of Chemistry, which also paid tribute to women in science and commemorated the centenary of the Nobel Prize awarded to Marie Curie. I was the only representative of Latin America in an international award for chemists and chemical engineers, in the field of natural products. In Brazil, a highlight was receiving the Sim\u00e3o Mathias medal, also in 2011, for researchers who make great contributions to chemistry. And in 2014 I received the Capes-Elsevier prize, based on my academic publications. It is an award for women from different areas of science, and I think it’s important that it was given to someone in the field of natural products because in chemistry, as in other sciences, competition between fields to determine which are more relevant is common.<\/p>\n

How did you become interested in the chemistry of natural products?
\n<\/span><\/strong>It must be an atavistic legacy. I was born in a very small town called Santa Rita, near the city of Jo\u00e3o Pessoa, which had a textile factory and nothing else. My mother’s family was not poor. My father, of indigenous heritage, was very poor and very intelligent. He was a diesel engine mechanic. Despite never having taken technical classes, he had almost the same knowledge as a mechanical engineer. When I was learning how to read we moved to Cabedelo, a port city, and my mother decided that I would study in a fishing colony, on Formosa beach\u2014it was beautiful, with huge coconut trees. The school was on the beach and I, very curious, asked the teacher why the sea rose and fell. She said that we were too young to understand. I asked my mother the same thing and she, very Catholic, said it was God’s doing. I think that my love for nature began that way.<\/span><\/p>\n

But how did this lead to chemistry?
\n<\/span><\/strong>My father wanted all his children to go to college. In high school, I focused on science. I became interested in medicine and my father was so proud…imagine, a daughter becoming a physician! Then the University High School was founded in Jo\u00e3o Pessoa, and students who did well were well prepared for university entrance exams. I did well. My mother, in her own way, helped me a lot to get into the undergraduate medicine program. She embroidered quilts, dresses, did hand-made embroidery in the Portuguese style to help my father financially, and during that period embroidered until dawn, a maternal contribution allowing me to study late.<\/span><\/p>\n

And what was it like, studying medicine at UFPB?
\n<\/span><\/strong>I was disappointed. The first classes, in physiology and anatomy, were very theoretical, and I wanted something hands-on. At the same time, in the first year, I was fascinated by my biochemistry classes. At the end of the second year, I switched to pharmacy.<\/span><\/p>\n

Were you influenced by your biochemistry professors?
\n<\/span><\/strong>They were very important. I had a hematology professor, Jackson Medeiros, who spoke of biochemistry and chemistry in such an exciting way that I became more passionate about chemistry than about hematology. When I began studying pharmacy, I was in my element.<\/span><\/p>\n

Did your family complain?
\n<\/span><\/strong>Only my father resisted. He asked how I could leave medicine to become a pharmacist when they had no money to set up a pharmacy. For a person with less education, medicine, engineering and law are the careers with the most status.<\/span><\/p>\n

Did you already know that you would become a researcher?
\n<\/span><\/strong>No, I performed clinical analyses, I worked on-call in the emergency room, and I only realized that I wanted to do research when I began to study pharmacognosy, a basic class for pharmacy majors. At that time the university was undergoing transformations and visiting professors came to Para\u00edba to teach organic chemistry. I took classes with Lauro Barata, from Unicamp, who at the time must have been a post-doc at the Federal University of Rio de Janeiro (UFRJ), and with Therezinha Tomassini, then a professor in the field of natural products at UFRJ, and with Roberto Cisne, professor at the Military Institute of Engineering (IME) in Rio de Janeiro. They were very good, they spoke with passion about the chemistry of plants, and that sparked my interest. The inclination I already had thus consolidated during my undergraduate studies.<\/span><\/p>\n

When did you decide to come to S\u00e3o Paulo?
\n<\/span><\/strong>That decision was also inspired by my teachers, among them my clinical analysis professor, Wilmar Nunes de Brito, one of the few at UFPB who had completed master’s degrees at that time. He had studied at the USP Institute of Chemistry (IQ-USP) under Paulo de Carvalho. He was intellectually fascinating, somewhat fatherly, and encouraged me by saying I thought like a scientist. He sent a letter of recommendation to Professor Carvalho, who responded by saying he would be pleased to welcome me as a graduate student, but I would have to pass a test. That was the first step. In the Northeast we always debated whether to go to S\u00e3o Paulo or Rio de Janeiro. Professor Paulo de Carvalho told me that S\u00e3o Paulo had better infrastructure for research. So there I went, with the insecurity of a person leaving their home at 22.<\/span><\/p>\n

Did you get a scholarship?
\n<\/span><\/strong>No, I came with nothing but courage. My family had a meeting and my father said that he would do whatever necessary to support me during the first few months, but after that I needed to obtain a scholarship or work to support myself. When I arrived, I stayed at a tiny inn on Teodoro Sampaio Street. Then I spent a few weeks in Edna’s home on Fradique Coutinho Street. She is Mary Coeli’s sister and the sister-in-law of Saulo Almeida de Ata\u00edde, who is now director of the Napole\u00e3o Laureano Hospital, the cancer hospital in Jo\u00e3o Pessoa. Then I moved to the USP dorms.<\/span><\/p>\n

That was in 1975?
\n<\/span><\/strong>Exactly. When I went to enroll in the master’s program at IQ-USP, I was met with the harsh reality that even today serves as a contrast between the rich Southeast and the poor Northeast. At USP and in S\u00e3o Paulo I faced prejudice against people from the Northeast. They thought we had inferior undergraduate qualifications\u2014mine was not, my training was excellent. My plan was to work with Paulo de Carvalho, but he didn’t work with the chemistry of natural products, but rather pharmaceutical chemistry. However, I wanted to do a master’s at USP even if it was not in my preferred specialty. At the dorms, I shared a room with a biology student from Rio Grande do Sul who was already an assistant professor. One day we were talking and she had an epileptic seizure. I freaked out, I didn’t know what to do. It was on a weekend, and there was no one around, and I became so anxious. Another tragic event was that, soon after I arrived, Paulo de Carvalho died of a heart attack. I was desperate when I heard the news.<\/span><\/p>\n

You didn’t know what to do.
\n<\/span><\/strong>I thought, “I’ll go home.” But I couldn’t, it would be admitting to failure. At the time, making a phone call was difficult, and my mother sent me a telegram: “Keep calm and stay strong.” I returned to the Institute of Chemistry to speak with the coordinator and choose another advisor. Then, as fate would have it, someone in the hallway asked me if I was looking for someone. It was Professor M\u00e1rio Motidome, a professor of the chemistry of natural products. He invited me to go to his office and I told him what had happened. He and Professor Carvalho were good friends and everyone in the department was traumatized. The research laboratories were all in building 11, B-11: upstairs, pharmaceutical chemistry, and downstairs, the chemistry of natural products with Professor Otto Gottlieb, who was already very famous. I began working on my first research project with Motidome, on a plant with a difficult name, <\/span>Mikania hirsutissima<\/i>. It seemed like my horizons had expanded, it was a very good time in my life. Since I had to study in order to be accepted into the master’s program, he said I could spend some time there to get used to the environment. I attended undergraduate courses in physical chemistry and inorganic chemistry to prepare for the exam. During that period, I ran into Professor Otto Gottlieb several times and I thought I would like him to be my advisor. But, in order to introduce myself to him, I had to show that I was a good student and pass the exam.<\/span><\/p>\n

What was your routine like?
\n<\/span><\/strong>I studied, prepared data, prepared chromatography plates, learned how to purify substances\u2014all basic tasks, but fundamental to the research I wanted to do. Professor Gottlieb, the head of the laboratory, was brilliant, very precise and methodical, both very important characteristics in a scientist. The laboratory was messy, but the plates and everything else had to be properly identified. I had a research notebook in which I recorded everything, and still have to this day. It is funny that I am sort of messy, but I force my students to be organized, and they must have research notebooks. S\u00e3o Paulo was a great school and showed me all of the contradictions in Brazil, including the excellent, wonderful professors that I met and who remained friends. One was Hans Viertler, who also worked at FAPESP and is now retired. He taught stereochemistry, which is important for understanding molecular structures and their properties. He would go out for beers with us, and was a great lecturer. We would often stay out until late talking about non-scientific topics and even soccer. He would play on the grass in front of the Institute of Chemistry with Jorge, who I later married. He was a fascinating, kind teacher. Living in the dorms, on almost no money, I caught pneumonia and was going to drop out, but he encouraged me to stay. I rested, taking medication and eating properly, and he would send me the class notes and homework, so I would not fall behind. It was due to his generosity that I did not have to repeat the course.<\/span><\/p>\n

His support was important?
\n<\/span><\/strong>Very. My master’s was a period of intense personal growth. I met Jorge and had enriching discussions at the Rei das Batidas bar, near USP. Despite being a pharmacist and a chemistry student, I had an open mind, a political spirit, social openness and friends studying geography, sociology, engineering and chemistry. The discussions with peers from other fields were rich, providing information with education, which differentiated us from some students today, who have a lot of information but little education.<\/span><\/p>\n

What was the topic of your master’s thesis?
\n<\/span><\/strong>A Euphorbiaceae from the Amazon, different from the usual Lauraceae and Myristicaceae that Professor Gottlieb studied.<\/span><\/p>\n

What is special about them?
\n<\/span><\/strong>They are rich in C6-C3 dimers, lignoids, which are biologically important phenolic substances. The C6-C3 monomers are the molecules that make up the structure that supports plants, the lignins. Gottlieb even differentiated between the lignoids, classifying them as lignans and neolignans, according to the biosynthetic pathway. Massuo Kato, of the USP Chemistry Institute, is trying to prove this classification by studying Piperaceae. They are important to a plant’s defense. Since these substances are biologically active, some are models for drugs.<\/span><\/p>\n

Gottlieb wanted to understand the structure of the lignans?
\n<\/span><\/strong>Not just the structure; he wanted to relate chemistry to biological and taxonomic characteristics. As a chemist, he already understood at that time that the secondary metabolites are essential to understanding the biology and phylogeny of plants. He was a great defender of chemical taxonomy and showed that chemistry corroborates taxonomy. He thus contributed a lot to the phylogeny of plants. He was a pioneer in this field in Brazil. The modern chemistry of natural products owes much to Professor Gottlieb, here, and to Professors Bem Gilbert and Walter Mors, at UFRJ. The three trained an entire generation of researchers in Brazil. Professor Gottlieb was the only Brazilian nominated for the Nobel prize twice. When I joined the laboratory, he was a full professor and had assistants to take care of students\u2014I was assigned to Marden Alvarenga, a very important person in my training. He was incisive and, as I was from the Northeast and timid, he gave me strength. I studied an Amazonian plant of the genus <\/span>Croton<\/i>, of the Euphorbiaceae family, which I have returned to studying now because of its peptides. It was outside Gottlieb’s focus.<\/span><\/p>\n

What led you to it?
\n<\/span><\/strong>Marden had done his dissertation on this family of plants and discovered some very distinct terpenes, containing bromine, which is common in marine organisms. I managed to isolate an unknown substance, and he insisted: “Purify it because it is impure.” At that time, elucidating the structure of a new substance was a huge challenge. Since we worked with phenolic compounds, the signals seen in the nuclear magnetic resonance (NMR) spectra at 60 megahertz appeared to be impurities. The more I purified it, the less I had to work with and the spectral magnetic resonance features remained the same. After about six months Professor Gabor Lukacs came to UFRJ. He was a specialist in the NMR of carbon 13, which was new then. I spent a week in Rio. When I came back, I proposed the structure of diterpene and we sent the substance to Hugo Gottlieb, Professor Gottlieb’s son, who was already a professor at the Weizmann Institute in Israel. His response was that there were no impurities. The substance had a furan nucleus and was a completely different terpene. I defended my thesis on this substance, which was unknown and very different. It took a while to determine and publish its correct structure. By that time, in the United States they were already starting to compile data on natural products in order to create software for natural product structures. The famous professor Carl Dejerassi sent a letter to Professor Gottlieb asking for data on diterpene in order to include this molecule, diasin, in the compilation of spectral data for editing the molecular structure prognostic software programs.<\/span><\/p>\n

What is diasin?
\n<\/span><\/strong>It is the substance that I isolated, a rearranged labdane diterpene, a class of molecules with 20 carbon atoms. Diterpenes are secondary metabolites, an adjective that is due to the belief that they were the wastes of primary metabolic pathways and had no function. These substances are important in regulating the functioning and defense of plants and other organisms. Nature does not waste energy producing something useless. Natural products such as lignans, flavonoids, diterpenoids, alkaloids, iridoids, and others which are very important for the regulation, defense and equilibrium of nature are formed via different metabolic pathways. These metabolic pathways are not random. Genetic characteristics influence the types of chemical reactions that occur in different species and allow us to classify plants on the basis of the metabolites they produce. There are certain classes of compounds that occur only in certain species of plants and serve as markers. That was what I did in my PhD in chemical taxonomy, an important tool for understanding plants and their phylogeny.<\/span><\/p>\n

Did you begin your PhD as soon as you finished your master’s?
\n<\/span><\/strong>I married and was pregnant with my first daughter when I finished my master’s. At around that time I was offered the opportunity to work at the Federal University of Para\u00edba. My daughter was born in March and I went to Para\u00edba May 5, as visiting professor. It was a way to return to my university and my family. We lived at the seashore, which was wonderful. But then we had adaptation problems: Jorge complained that the morning newspaper arrived at night, that the bookstore did not have the books he wanted… He was from S\u00e3o Paulo, and living in tiny Jo\u00e3o Pessoa in the late 1970s was not easy. Then a chance to return arose, he got a job with Phebo. I called Professor Gottlieb and said I would return for a doctorate. At that point my academic history became intertwined with my personal history: I was on the flight back to S\u00e3o Paulo with my daughter, Mariana, in my lap and the woman who sat next to me, Maria Aparecida Pouchet Campos, was from Capes and Dean of the Unesp School of Pharmaceutical Sciences in Araraquara. Mariana was a sweetie and Maria began to play with her. Later, she gave me a card and said that all she wanted in pharmacognosy was someone who worked with Otto Gottlieb. Since we were coming to S\u00e3o Paulo anyway, I decided to go visit Araraquara. When I arrived, I was greeted by the chemists who had been in the master’s program with me. They were excited. So I decided to teach pharmacy there.<\/span><\/p>\n

How did you juggle a doctorate at USP with teaching classes in Araraquara?
\n<\/span><\/strong>I hadn’t started yet. We went to Araraquara where there was a possibility of creating a master’s degree program in rural and urban sociology and Jorge wanted to study with Maria Aparecida de Moraes Silva, who was in S\u00e3o Carlos. It was an opportunity for us to return together to S\u00e3o Paulo, with jobs. His father had a cosmetics company in Diadema, which went bankrupt. Anyway, Jorge said that we would be able to manage because it was close by\u2014it wasn’t, but we were young and thought it was.<\/span><\/p>\n

What was your academic life like in Araraquara?
\n<\/span><\/strong>I started working on my projects in pharmacy with great excitement. The first was with Rubiaceae, the plant I was studying during my master’s degree. But that did not work, because I had to do a doctorate and Professor Gottlieb said: “Since you have a child and cannot travel a lot, do a theoretical dissertation. Let’s see what information these molecules provide about the evolution and phylogeny of plants, and what contributions we can make to botany, taxonomy and biology.” So I left the lab and did theoretical work, which was good for my training. It was a promising period. In 1990 I won a scholarship from the German Academic Exchange Service (DAAD) and spent a month in Germany.<\/span><\/p>\n

What was your PhD research on?
\n<\/span><\/strong>I studied the full Gentianales order and we did a beautiful study on the evolution of indole alkaloids in nature. The work Professor Gottlieb and I did on that theme in the Rubiaceae taxon was a success. There was a renowned taxonomist, Elmar Robbrecht, who was creating a new taxonomy for the Rubiaceae family, something complex from a biological standpoint, for this family of plants that occurs worldwide and whose products are of high economic value. He was delighted because, using only chemical data, we came to the same conclusions as those in his new taxonomy. He wrote an article in a famous journal, cited our work and invited us to an international conference in Belgium. I was so nervous, as it was the first time I was going abroad to give a 50 minute talk and I was still sort of a student.<\/span><\/p>\n

Did this paper guide your research career?
\n<\/span><\/strong>I was more determined than ever to establish a new line of research. Talking to Professor Gottlieb, he said there was no one working on the marine environment and that I could I do a post-doctorate in that field and direct my research into something completely different. I was excited, but then my life became a disaster: Jorge had an ischemic stroke at age 38 and became very ill. I had to stop everything. I withdrew from the university and, when I returned, I no longer wanted to work with the marine environment.<\/p>\n

Did you stay here or in Araraquara during this phase?
\n<\/span><\/strong>Here and there. First, Jorge was at the Albert Einstein Hospital. Then he stayed at his mother’s house because he needed physiotherapy and care. I came back every Friday and returned Tuesday.\u00a0 On one of the trips, I had a car accident, and the car flipped who knows how many times. I didn’t die only because it was not my time yet. During that period, I spent a lot of time in Massayoshi Yoshida’s laboratory at USP.<\/span><\/p>\n

Did you ask for time off at Araraquara in order to concentrate on research?
\n<\/span><\/strong>During the first six months, I took a complete leave of absence. I had to look after Mariana and Tiago, who were still small. I was afraid of losing my job and continued to teach classes, but I practically stopped doing research. But Jorge improved a lot and said I should not destroy my career. I was not sure, but I agreed and went with our two children to the United States in 1992, which was also a great experience for them. I did my post-doctorate work at Virginia Tech, with David Kingston.<\/span><\/p>\n

Did your husband return to work?
\n<\/span><\/strong>No, he was unable to. He did a lot of volunteer work, because there were times in which he was fine and could talk about Karl Marx’s work from top to bottom. Then, he would suffer a sudden loss of cognition and couldn’t. He died at 60. We fought through this for 22 years. At the end, he became a bit of a hippie, an adventurer. He loved the state of Bahia and in the end he lived there, in an inn in Valen\u00e7a. In 2011, the International Year of Chemistry, I was in Paris when he became ill in Bahia and a friend called to let me know. He was transferred to the city of Salvador, and after a heart attack he had to come back to S\u00e3o Paulo. During that period, until his death in September of that year, I stayed mostly in S\u00e3o Paulo.<\/span><\/p>\n

Meanwhile, you developed a long career.
\n<\/span><\/strong>It was a struggle, but it was rewarding. We were starting a graduate program and I decided I wanted to set up a model laboratory for the chemistry of natural products. I needed a team in order to do that. I rolled up my sleeves and was the first to work on the chemistry of natural products and phylogeny at IQ-Unesp. If you have quality basic science, you can work with the best aspects of the chemistry of natural products and collaborate with people in pharmacology, toxicology and biology to try to find a biomolecule with practical applications. We began to develop projects with this focus.<\/span><\/p>\n

When was this?
\n<\/span><\/strong>In 2000. I worked on Aristolochiaceae for some time with Professor Lucia Xavier Lopes, but soon moved to Rubieaceae and obtained my first research grant from FAPESP. Then Marcia Nasser and Maysa Furlan and other colleagues came. Now there are seven working at the Center for Natural Product Bioassays, Biosynthesis and Eco-physiology (NuBBE). Here, the chemistry of natural products was very traditional: isolate something, determine its structure, and publish. We wanted to understand nature better, to try to find a relationship between biosynthesis and the function of the macromolecules in plants and also their pharmacological function. Each day we are more convinced that nature, throughout the ages, has not produced such a sophisticated chemical laboratory to synthesize hundreds of substances with no function. There are biologically active compounds that we can use as prototypes for drugs. But Mother Nature did not do this for humans. She produces these compounds for self-preservation and to maintain equilibrium. We began to structure our laboratory with this focus. With Alberto Cavalheiro, who is brilliant at separation methods, NuBBE developed an excellent analytic platform for natural products, mainly because our laboratory is now green. Angela, Dulce and Ian were the last members to join the NuBBE team.<\/span><\/p>\n

What is a green laboratory?
\n<\/span><\/strong>A sustainable laboratory. We do not use chlorinated products, or toxic solvents. Everyone sad bad things about the chemistry of natural products because it was dirty chemistry. To isolate a few milligrams of a pure substance, we used a lot of chlorinated and organic solvents, which are toxic and accumulate in nature. Separation methods using ethanol, water and acetone were recently successfully developed by Cristiano, a post-doctoral researcher supervised by Alberto.<\/span><\/p>\n

How long have you been green?
\n<\/span><\/strong>Three years. We have a very well-equipped laboratory due to the Biota program. In 1998, when we were setting up the laboratory, during the first meetings with Sonia Dietrich, she invited me to attend a Biota program meeting in Campinas. She said I was in a good position to submit a Biota proposal in the chemistry of natural products.<\/span><\/p>\n

Was that BioProspecta?
\n<\/span><\/strong>It later became that. At first it was a unique project for bioprospecting substances in the Amazon and the Cerrado. It was my first thematic project. We were able to perform very well organized species collection and buy high-resolution mass spectrometry equipment.<\/span><\/p>\n

You did the analyses.
\n<\/span><\/strong>We did the chemical analyses and the folks in pharmacy and botany did the activity analyses.<\/span><\/p>\n

In animals or in cells?
\n<\/span><\/strong>We did in vitro tests. It was during that period that we were able to train highly qualified staff and form international partnerships. We were able to carry out studies not only in phytochemistry, of compounds produced by plants, but also of the endophytic fungi that live inside plants, and of seaweed, coordinated by Angela and Dulce. We didn’t do just analysis, but also biosynthesis, coordinated by Maysa, and ecology, managed by Alberto and Ian. We are interested in seeing how these substances behave in plants. Now, before I retire, I’m building a group interested in the peptides produced by plants. Few people study this in Brazil. Peptides perform many important functions. Some fight malaria, Chagas disease or tumors. I am interested in understanding their function in the parts of the plants where they are produced. We are working with plants from the Caatinga, a very dry environment. If we can prove that these peptides are responsible for how stomata function and allow these plants to survive in these environments, this will be very important to understanding the ecosystem.<\/span><\/p>\n

If you come to the conclusion that, in fact, the stomata prevent water loss, you will understand a self-preservation mechanism used in extreme environments.
\n<\/span><\/strong>Exactly. We need to show how plants persevere in these environments. There are few studies on Brazilian plants and our environment.<\/span><\/p>\n

In addition to international partnerships, did you also do multidisciplinary research? What was your experience like?
\n<\/span><\/strong>I always thought that chemistry was a central and plural science. And no one knows everything, so collaboration is fundamental. We set up Brazilian groups in biology, physics, and principally in pharmacology. The work with Glaucius Oliva’s group was interesting, because he’s a physicist working on protein synthesis and has extensive experience with databases. The partnership with him came through our work with Adriano Andicopulo. One day I told him I wanted to create a database for the 640 substances we had already isolated. I wanted to make all of the data available so people, companies and universities could access it.<\/span><\/p>\n

What is the database called?
\n<\/span><\/strong>The NuBBE database. It’s very popular abroad, but few people access it from Brazil.<\/span><\/p>\n

And this database began to be developed recently?
\n<\/span><\/strong>A year and a half ago. I had the idea but didn’t know how to implement it, hence the importance of collaboration. I had a bright student who planned to do a PhD in medicinal chemistry. We found an IT person and he set up the computer system. We created an open system in which we can store a lot of information. There are many databases of traditional natural products containing data on the species and family of plants, the structure of the compounds and physical chemical information. The medicinal chemistry databases normally contain other properties that are important for pharmacology. Our database is different because it includes both.<\/span><\/p>\n

Are you interested in having these molecules reach the cosmetics and drug industries?
\n<\/span><\/strong>I spoke to Jo\u00e3o Batista Calixto, at the Federal University of Santa Catarina, who is interested in some of them. He coordinates the CIEnP, a center for preclinical research, and wants to start tests with plants that we studied. I cannot talk about it now. We applied for a patent for one and we are in the proof of concept process. We have already formed partnerships with companies. One didn’t work out.<\/span><\/p>\n

It was for a molecule with a potential effect on Alzheimer’s disease, right?
\n<\/span><\/strong>That molecule was a reversible inhibitor of the enzyme acetylcholinesterase. We signed a collaboration agreement with Apsen, a pharmaceutical company that manufactures products to fight neurodegenerative diseases. They invested in the first non-academic studies, but decided to discontinue the research. This happens with many molecules,\u00a0 both here and abroad.<\/span><\/p>\n

Was there some complication in the manufacturing phase?
\n<\/span><\/strong>It is one thing to develop a phytotherapeutic substance, which is an extract, a standardized mixture that must undergo pharmacological, efficacy and safety tests. It is another to reach production scale for a phytotherapeutic drug, a pure substance. In order to avoid devastating the environment, the substance, which has a complex molecular structure that the plant produces by the milligram, must be synthesized in a laboratory. This is fundamental, but not trivial. I think that is why that project, with that molecule, did not go forward.<\/span><\/p>\n

And now?
\n<\/span><\/strong>They discontinued work and allowed us to present the idea to another company. Calixto is interested in it if we modify it in order to use it to fight neuropathic pain. But we were unable to collect the plant to obtain material and alter its structure.<\/span><\/p>\n

Do you interact with the cosmetics industry?
\n<\/span><\/strong>We had two projects with Natura, one through Finep and another through FAPESP. Proof of concept is important so that the company can absorb what we have. They begin, but then give up.<\/span><\/p>\n

Are the preclinical trials the problem?
\n<\/span><\/strong>Yes. They’re harder to do in Brazil. Now, with this laboratory, with an international standard of quality, this phase might also be easier. Brazilian companies may be interested, and also multinationals. I see no problem with this, as long as the agreements are well structured. That is what China does.<\/span><\/p>\n

Why don’t we advance?
\n<\/span><\/strong>It is a policy problem. We have FAPESP at the state level, with the PIPEs (Innovative Research in Small Businesses Programs), PITEs (Partnerships for Technological Innovation) and now the RIDCs (Research, Innovation and Dissemination Centers). At the federal level, there is the “Lei do Bem”, a set of tax incentives for R&D to boost innovation (No. 11.196\/05), but we need to awaken a new mentality in Brazilian businesses. In the cosmetics industry, we have Natura, an important Brazilian company with a lot of projects, but they have not incorporated radical innovations in terms of releasing products based on hard science. L’Or\u00e9al, which is setting up offices in Rio, has always focused on synthesis, and is trying to change in Brazil. It has very sophisticated laboratories in the European Union, the United States, and Asia, and high-level researchers who publish their results in scientific journals in the field. Our biodiversity is a huge arsenal that could be used. At a SBPC (Brazilian Society for the Advancement of Science) meeting, I gave a lecture on sustainable development of the Amazon, which is purely extractive now. We need to take that step beyond extractionism, but we have not. Our pharmaceutical industry is very small. The multinationals dominate and carry out research in laboratories in their home countries.<\/span><\/p>\n

Couldn’t we do that?
\n<\/span><\/strong>We could, but we would need to have support from the Brazilian government. FAPESP created a 10-year cooperation program with GlaxoSmithKlein, which is starting to carry out basic and applied research and is advancing. There is also the INCT (Brazilian National Institute of Science and Technology) model. Perhaps, in the future, we can do it too. We are the country of the future.<\/span><\/p>\n

Are there pieces missing along the way?
\n<\/span><\/strong>Now we have innovation agencies that create bridges. In the state of S\u00e3o Paulo, we have a favorable environment for quality research and for working with companies in order to transfer research into applications.\u00a0 The pharmaceutical industry is high risk. The cost of doing business in Brazil is very high and discourages the entrepreneur from investing in risk constantly.<\/span><\/p>\n

Do we need to reach the clinical trial phase before companies become interested?
\n<\/span><\/strong>The more advanced, the easier it is to form a partnership. Why is it easier abroad? Why doesn’t a Brazilian company set up a research laboratory and take this step?\u00a0 It would be an enormous differential for it and for Brazil. The multinationals have well-equipped laboratories abroad.<\/span><\/p>\n

But only the large companies can do this?
\n<\/span><\/strong>If there were a mechanism to decrease the cost, this could generate employment for well-trained PhDs, because there is no more space in the universities, and the company would be able to carry out its own research, as at Glaxo and Merck. Some are starting, like Natura and Crist\u00e1lia, but they are a long way from advancing in this competitive environment. Who wins? China.<\/span><\/p>\n

But don’t China and India do a lot of “me too”? Drugs based on alterations of known molecules, and not innovative drugs?
\n<\/span><\/strong>But you need expertise even to do “me too” development. China invests a lot in this. They have a lot of researchers and they work like ants, like in Japan, which develops good things now, whereas before they only copied. It is related to our cultural disorganization, and our pool of trained personnel is still small.<\/span><\/p>\n

In parallel with your research, you were politically active in the scientific community. You were president of the Brazilian Chemical Society.
\n<\/span><\/strong>The first woman. In our field, there are plenty of women in undergraduate, master’s and PhD programs. But the number of women who rise in the career is small.<\/span><\/p>\n

Shouldn’t this scenario change with the increase in the number of women in the initial stages of the system?
\n<\/span><\/strong>The numbers have been increasing over the last 40 years, but we are still not there. There is a cultural component, machismo, which we women also share. I know women who are very good, but they shy from the limelight and let men take more credit. It is complicity to maintain their marriages and their families.<\/span><\/p>\n

So women do not fight to reach high positions, or they are barred from them?
\n<\/span><\/strong>They move up, but perhaps they are less competitive than men. Or less effective in competing. I think there is a cultural component barring creativity in girls and saying that physics, chemistry and mathematics are for boys.<\/span><\/p>\n

What was it like being president of the SBQ?
\n<\/span><\/strong>They were two very rewarding years. We strengthened international partnerships. We have several programs with the American Chemistry Society, the Royal Society of Chemistry and the International Union of Pure and Applied Chemistry (IUPAC). We are going to host the 2017 IUPAC conference in Brazil. This is the most important conference and it will be held in South America for the first time. It will be in S\u00e3o Paulo.\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"Research seeks international cooperation and investigates molecules","protected":false},"author":16,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[161],"tags":[211,213,259,232],"coauthors":[105,124],"class_list":["post-156295","post","type-post","status-publish","format-standard","hentry","category-interview","tag-biochemistry","tag-botany","tag-chemistry","tag-pharmacology"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/156295","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=156295"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/156295\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=156295"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=156295"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=156295"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=156295"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}