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Biomolecules from plant species of remnant areas of the Atlantic Forest and Cerrado to treat neglected tropical diseases - chemical and pharmacological aspects

Grant number: 18/07885-1
Support type:BIOTA-FAPESP Program - Regular Research Grants
Duration: August 01, 2018 - July 31, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:João Henrique Ghilardi Lago
Grantee:João Henrique Ghilardi Lago
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
Assoc. researchers:André Gustavo Tempone Cardoso ; Joao Luiz Baldim Zanin ; Luiz Felipe Domingues Passero ; Patricia Sartorelli
Associated grant(s):19/13906-4 - Discovering new drug leads against Chagas Disease Based on Brazilian bioactive plant molecules, AP.R SPRINT

Abstract

In the present project will be selected plant species from Sao Paulo State biomes (Atlantic Forest and "Cerrado") aiming the structural characterization of natural products/semisynthetic derivatives with antiparasitic activity as well as evaluation of pre-clinical and toxicological potential, in continuation to the study begun in 2015 with FAPESP funding (project 2015/11936-2). Thus, different species belonging to Lauraceae, Piperaceae and Asteraceae will be collected and their extracts prepared, and those who had proven antiparasitic action (antileishmanial and antitrypanosomal) will be subjected to molecular dereplication procedures (HPLC/MS and NMR) followed to a bioassay-guided fractionation processes. Using this approach, the active metabolites will be purified and their structures will be determined by spectroscopic/spectrometric techniques. After this step, the crude extracts will be standardized by HPLC/DAD and HPLC/MS allowing the identification of the bioactive compound in the vegetable matrix (biomarker). After the recognition of the active substances, they will be submitted to SAR tests through different techniques aiming at the improvement of biological activities by molecular modifications guided by multivariate statistics and prediction models created according to each class of compounds obtained. Additionally, it is intended, in this proposal, to carry out specific tests to define the mode of action of substances with proven antiprotozoal activity in relation to the parasite, especially membrane pore evaluation and ultrastructural studies. Following the standardization biological assays will be carried out. Thus, this project intends to add new compounds and / or extracts with proven herbal pharmacological armamentarium to restricted activity, providing tools for the development of new herbal drugs. (AU)

Scientific publications (26)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
JESUS, JESSICA ADRIANA; FRAGOSO DA SILVA, THAYS NICOLLI; YAMAMOTO, EDUARDO SEIJI; G. LAGO, JOAO HENRIQUE; DALASTRA LAURENTI, MARCIA; PASSERO, LUIZ FELIPE DOMINGUES. Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis. PATHOGENS, v. 9, n. 10 OCT 2020. Web of Science Citations: 0.
YAMAMOTO, EDUARDO SEIJI; DE JESUS, JESSICA ADRIANA; BEZERRA-SOUZA, ADRIANA; BRITO, JULIANA R.; LAGO, JOAO HENRIQUE G.; LAURENTI, MARCIA DALASTRA; PASSERO, LUIZ FELIPE DOMINGUES. Tolnaftate inhibits ergosterol production and impacts cell viability of Leishmania sp.. BIOORGANIC CHEMISTRY, v. 102, SEP 2020. Web of Science Citations: 0.
UMEHARA, ERIC; SILVA, THAIS A. COSTA; MENDES, VIVIANE M.; GUADAGNIN, RAFAEL C.; SARTORELLI, PATRICIA; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G. Differential lethal action of C17:2 and C17:0 anacardic acid derivatives in Trypanosoma cruzi - A mechanistic study. BIOORGANIC CHEMISTRY, v. 102, SEP 2020. Web of Science Citations: 0.
DE SOUSA, FERNANDA S.; BALDIM, JOAO L.; AZEVEDO, RICARDO A.; FIGUEIREDO, CARLOS R.; PIEPER, PAULINE; SEAR, CLAIRE E.; ANDERSON, EDWARD A.; LAGO, JOAO HENRIQUE G. Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design. Bioorganic & Medicinal Chemistry Letters, v. 30, n. 16 AUG 15 2020. Web of Science Citations: 0.
BARBOSA, HENRIQUE; DA SILVA, RAFAEL LEONARDO C. G.; COSTA-SILVA, THAIS A.; TEMPONE, ANDRE G.; ANTAR, GUILHERME M.; LAGO, JOAO HENRIQUE G.; CASELI, LUCIANO. Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface. BIOORGANIC CHEMISTRY, v. 101, AUG 2020. Web of Science Citations: 0.
SILVA, ARMENIO A. DE CARVALHO A. DA; SOUSA, ELCILENE A. DE; VERAS, MARCIA D. ALVES; ARAUJO, BRUNO Q.; THEVENARD, FERNANDA; LAGO, JOAO HENRIQUE G.; COSTA-SILVA, THAIS A.; TEMPONE, ANDRE G.; CHAVES, MARIANA H. In vitro anti-Trypanosoma cruzi evaluation of sesquiterpenes from the branches of Oxandra sessiliflora. PHYTOCHEMISTRY LETTERS, v. 37, p. 59-62, JUN 2020. Web of Science Citations: 0.
MENGARDA, ANA C.; MENDONCA, POLIANA S.; MORAIS, CRISTIANE S.; COGO, RAMON M.; MAZLOUM, SUSANA F.; SALVADORI, MARIA C.; TEIXEIRA, FERNANDA S.; MORAIS, THIAGO R.; ANTAR, GUILHERME M.; LAGO, JOAO HENRIQUE G.; MORAES, JOSUE. Antiparasitic activity of piplartine (piperlongumine) in a mouse model of schistosomiasis. Acta Tropica, v. 205, MAY 2020. Web of Science Citations: 0.
MORAIS, THIAGO R.; ALVES CONSERVA, GEANNE A.; VARELA, MARINA T.; COSTA-SILVA, THAIS A.; THEVENARD, FERNANDA; PONCI, VITOR; FORTUNA, ANA; FALCAO, AMILCAR C.; TEMPONE, ANDRE G.; FERNANDES, JOAO PAULO S.; LAGO, JOAO HENRIQUE G. Improving the drug-likeness of inspiring natural products - evaluation of the antiparasitic activity against Trypanosoma cruzi through semi-synthetic and simplified analogues of licarin A. SCIENTIFIC REPORTS, v. 10, n. 1 MAR 25 2020. Web of Science Citations: 0.
LONDERO, VINICIUS S.; COSTA-SILVA, THAIS A.; TEMPONE, ANDRE G.; NAMIYAMA, GISLENE M.; THEVENARD, FERNANDA; ANTAR, GUILHERME M.; BAITELLO, JOAO B.; LAGO, JOAO HENRIQUE G. Anti-Trypanosoma cruzi activity of costic acid isolated from Nectandra barbellata (Lauraceae) is associated with alterations in plasma membrane electric and mitochondrial membrane potentials. BIOORGANIC CHEMISTRY, v. 95, JAN 2020. Web of Science Citations: 0.
GRECCO, SIMONE DOS SANTOS; LETSYO, EMMANUEL; TEMPONE, ANDRE GUSTAVO; GHILARDI LAGO, JOAO HENRIQUE; JERZ, GEROLD. Electrospray mass-spectrometry guided target isolation of neolignans from Nectandra leucantha (Lauraceae) by high performance- and spiral-coil countercurrent chromatography. Journal of Chromatography A, v. 1608, DEC 20 2019. Web of Science Citations: 0.
BRITO, JULIANA R.; PASSERO, LUIZ FELIPE D.; BEZERRA-SOUZA, ADRIANA; LAURENTI, MARCIA D.; ROMOFF, PAULETE; BARBOSA, HENRIQUE; FERREIRA, EDGARD A.; LAGO, JOAO HENRIQUE G. Antileishmanial activity and ultrastructural changes of related tetrahydrofuran dineolignans isolated from Saururus cernuus L. (Saururaceae). Journal of Pharmacy and Pharmacology, v. 71, n. 12, p. 1871-1878, DEC 2019. Web of Science Citations: 0.
BRITO, JULIANA R.; DA COSTA-SILVA, THAIS A.; TEMPONE, ANDRE G.; FERREIRA, EDGARD A.; LAGO, JOAO HENRIQUE G. Dibenzylbutane neolignans from Saururus cernuus L. (Saururaceae) displayed anti-Trypanosoma cruzi activity via alterations in the mitochondrial membrane potential. Fitoterapia, v. 137, SEP 2019. Web of Science Citations: 0.
DA COSTA-SILVA, THAIS A.; ALVES CONSERVA, GEANNE A.; GALISTEO, JR., ANDRES J.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G. Antileishmanial activity and immunomodulatory effect of secosubamolide, a butanolide isolated from Nectandra oppositifolia (Lauraceae). Journal of Venomous Animals and Toxins including Tropical Diseases, v. 25, AUG 19 2019. Web of Science Citations: 0.
FERREIRA, DAIANE D.; SOUSA, FERNANDA S.; COSTA-SILVA, THAIS A.; REIMAO, JULIANA Q.; TORRECILHAS, ANA C.; JOHNS, DEIDRE M.; SEAR, CLAIRE E.; HONORIO, KATHIA M.; LAGO, JOAO HENRIQUE G.; ANDERSON, EDWARD A.; TEMPONE, ANDRE G. Dehydrodieugenol B derivatives as antiparasitic agents: Synthesis and biological activity against Trypanosoma cruzi. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 176, p. 162-174, AUG 15 2019. Web of Science Citations: 2.
MORAIS, THIAGO R.; COSTA-SILVA, THAIS A.; FERREIRA, DAIANE D.; NOVAIS, BIANCA J.; TORRECILHAS, ANA CLAUDIA T.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G. Antitrypanosomal activity and effect in plasma membrane permeability of (-)-bornyl p-coumarate isolated from Piper cernuum (Piperaceae). BIOORGANIC CHEMISTRY, v. 89, AUG 2019. Web of Science Citations: 1.
VARELA, MARINA T.; COSTA-SILVA, THAIS A.; LAGO, JOAO HENRIQUE G.; TEMPONE, ANDRE G.; FERNANDES, JOAO PAULO S. Evaluation of the antitrypanosoma activity and SAR study of novel LINS03 derivatives. BIOORGANIC CHEMISTRY, v. 89, AUG 2019. Web of Science Citations: 0.
OLIVEIRA, EMERSON A.; MARTINS, EUDER G. A.; SOARES, MARISI G.; CHAGAS-PAULA, DANIELA A.; PASSERO, LUIZ F. D.; SARTORELLI, PATRICIA; BALDIM, JOAO L.; LAGO, JOAO HENRIQUE G. A Comparative Study on Chemical Composition, Antileishmanial and Cytotoxic Activities of the Essential Oils from Leaves of Guarea macrophylla (Meliaceae) from Two Different Regions of Sao Paulo State, Brazil, Using Multivariate Statistical Analysis. Journal of the Brazilian Chemical Society, v. 30, n. 7, p. 1395-1405, JUL 2019. Web of Science Citations: 0.
GOMES, KAIO S.; DA COSTA-SILVA, THAIS A.; OLIVEIRA, IGOR H.; AGUILAR, ANDREA M.; OLIVEIRA-SILVA, DIOGO; UEMI, MIRIAM; SILVA, WENDER A.; MELO, LENNINE R.; ANDRADE, CARLOS KLEBER Z.; TEMPONE, ANDRE G.; BALDIM, JOAO L.; LAGO, JOAO HENRIQUE G. Structure-activity relationship study of antitrypanosomal chalcone derivatives using multivariate analysis. Bioorganic & Medicinal Chemistry Letters, v. 29, n. 12, p. 1459-1462, JUN 15 2019. Web of Science Citations: 0.
OLIVEIRA, EMERSON A.; BRITO, IVANILDO A.; LIMA, MARTA L.; ROMANELLI, MAIARA; MOREIRA-FILHO, JOSE T.; NEVES, BRUNO J.; ANDRADE, CAROLINA H.; SARTORELLI, PATRICIA; TEMPONE, ANDRE G.; COSTA-SILVA, THAIS A.; LAGO, JOAO HENRIQUE G. Antitrypanosomal Activity of Acetogenins Isolated from the Seeds of Porcelia macrocarpa Is Associated with Alterations in Both Plasma Membrane Electric Potential and Mitochondrial Membrane Potential. Journal of Natural Products, v. 82, n. 5, p. 1177-1182, MAY 2019. Web of Science Citations: 0.
AMARAL, MAIARA; DE SOUSA, FERNANDA S.; SILVA, THAIS A. COSTA; JUNIOR, ANDRES JIMENEZ G.; TANIWAKI, NOEMI N.; JOHNS, DEID RE M.; LAGO, JOAO HENRIQUE G.; ANDERSON, EDWARD A.; TEMPONE, ANDRE G. A semi-synthetic neolignan derivative from dihydrodieugenol B selectively affects the bioenergetic system of Leishmania infantum and inhibits cell division. SCIENTIFIC REPORTS, v. 9, APR 16 2019. Web of Science Citations: 3.
DE SOUSA, FERNANDA S.; NUNES, EMILENE A.; GOMES, KAIO S.; CERCHIARO, GISELLE; LAGO, JOAO HENRIQUE G. Genotoxic and cytotoxic effects of neolignans isolated from Nectandra leucantha (Lauraceae). TOXICOLOGY IN VITRO, v. 55, p. 116-123, MAR 2019. Web of Science Citations: 0.
GUIMARAES GONCALVES, GIULIA ELISA; MORAIS, THIAGO RAHAL; GOMES, KAIO DE SOUZA; COSTA-SILVA, THAIS ALVES; TEMPONE, ANDRE GUSTAVO; GHILARDI LAGO, JOAO HENRIQUE; CASELI, LUCIANO. Antitrypanosomal activity of epi-polygodial from Drimys brasiliensis and its effects in cellular membrane models at the air-water interface. BIOORGANIC CHEMISTRY, v. 84, p. 186-191, MAR 2019. Web of Science Citations: 0.
ALVES CONSERVA, GEANNE A.; DA COSTA-SILVA, THAIS A.; AMARAL, MAIARA; ANTAR, GUILHERME M.; NEVES, BRUNO J.; ANDRADE, CAROLINA H.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G. Butenolides from Nectandra oppositifolia (Lauraceae) displayed anti-Trypanosoma cruzi activity via deregulation of mitochondria. Phytomedicine, v. 54, p. 302-307, FEB 15 2019. Web of Science Citations: 1.
GONCALVES, GIULIA ELISA G.; MORAIS, THIAGO R.; LAGO, JOAO HENRIQUE G.; CASELI, LUCIANO. Incorporation of polygodial in Langmuir films of selected lipids. Thin Solid Films, v. 669, p. 19-28, JAN 1 2019. Web of Science Citations: 0.
SANTOS, BEATRIZ MENDES; BEZERRA-SOUZA, ADRIANA; ARAGAKI, SONIA; RODRIGUES, ELIANA; UMEHARA, ERIC; GHILARDI LAGO, JOAO HENRIQUE; LAURENTI, MARCIA DALASTRA; RIBEIRO, SUSAN PEREIRA; DOMINGUES PASSERO, LUIZ FELIPE. Ethnopharmacology Study of Plants from Atlantic Forest with Leishmanicidal Activity. Evidence-based Complementary and Alternative Medicine, 2019. Web of Science Citations: 0.
GRECCO, SIMONE S.; COSTA-SILVA, THAIS A.; SOUSA, FERNANDA S.; CARGNELUTTI, STEFANO B.; UMEHARA, ERIC; MENDONCA, POLIANA S.; TEMPONE, ANDRE G.; LAGO, JOAO HENRIQUE G. Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, SEP 27 2018. Web of Science Citations: 0.

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