Antiinfective compounds: an evolution in the medicinal chemistry of leishmanicidal tiazoles and the search for new tuberculostic agents

• Grant number: 12/20990-2
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: May 31, 2015
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Flavio da Silva Emery
• Grantee: Flavio da Silva Emery
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated researchers: Maria Cristina Nonato

Abstract

This proposal is focused on aspects of chemical biology and medicinal chemistry targeting infectious diseases. Among the main objectives we highlight the development of new lead compounds and molecules useful as proof of concept for leishmaniasis and tuberculosis. For leishmaniasis will be evaluated the inhibition of the enzyme diidroorotato dehydrogenase, an enzyme involved in de novo biosynthesis of pyrimidines, a biochemical pathway crucial to the parasite, in continuation of the preliminary studies (FAPESP 2009/14184-0). Approaches based on the structure of the ligand and on structural fragments will be applied, inspired by the basic structure of previously described inhibitors of the type 2-amino-naftotiazol. For TB, we will explore the prior description of tuberculostatic activity of a natural cyclic peptide - rufomycin B, aiming to develop a study of structure-activity relationship to obtain compounds with greater efficacy, safety and elucidating the mechanism of action. In this sense, will be emphasized the solid phase synthesis of the natural product and a library of analogues. An overview of the proposal indicates an intersection between organic synthesis and medicinal chemistry to obtain useful information for the development of bioactive molecules for neglected tropical diseases. (AU)

Scientific publications

(11)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

SILVA JUNIOR, P. E.; REZENDE, L. C. D.; GIMENES, JULIA POSSAMAI; MALTAROLLO, VINICIUS GONCALVES; DALE, JAMES; TROSSINI, G. H. G.; EMERY, F. S.; GANESAN, A.. Synthesis of two `heteroaromatic rings of the future' for applications in medicinal chemistry. RSC ADVANCES, v. 6, n. 27, p. 22777-22780, 2016. (11/23342-9, 12/20990-2, 13/26485-0)

DIAS DE REZENDE, LUCAS CUNHA; GIL DE MELO, SHAIANI MARIA; BOODTS, STIJN; VERBELEN, BRAM; DEHAEN, WIM; EMERY, FLAVIO DA SILVA. Thiocyanation of BODIPY dyes and their conversion to thioalkylated derivatives. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 13, n. 21, p. 6031-6038, 2015. (13/24408-9, 11/23342-9, 12/20990-2)

PERES, RAPHAEL S.; SANTOS, GABRIELA B.; CECILIO, NERRY T.; JABOR, VALQURIA A. P.; NIEHUES, MICHAEL; TORRES, BRUNA G. S.; BUQUI, GABRIELA; SILVA, CARLOS H. T. P.; DALLA COSTA, TERESA; LOPES, NORBERTO P.; et al. Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis. ARTHRITIS RESEARCH & THERAPY, v. 19, MAR 7 2017. (13/08216-2, 12/20990-2, 09/54014-7, 12/25075-0, 14/50265-3)

SILVA JUNIOR, P. E.; REZENDE, L. C. D.; GIMENES, JULIA POSSAMAI; MALTAROLLO, VINICIUS GONCALVES; DALE, JAMES; TROSSINI, G. H. G.; EMERY, F. S.; GANESAN, A.. Synthesis of two 'heteroaromatic rings of the future' for applications in medicinal chemistry. RSC ADVANCES, v. 6, n. 27, p. 4-pg., 2016-01-01. (11/23342-9, 13/26485-0, 12/20990-2)

FUMAGALLI, FERNANDO; EMERY, FLAVIO DA SILVA. Pd(II)-mediated cyclodehydrogenation of formyldiarylamines-total synthesis of natural carbazoles clauraila A, clausenal and 6-methoxymurrayanine. Tetrahedron Letters, v. 56, n. 18, p. 2307-2310, APR 29 2015. (12/20990-2, 13/00727-8)

MALTAROLLO, VINICIUS G.; HONORIO, KATHIA M.; EMERY, FLAVIO S.; GANESAN, ARASU; TROSSINI, GUSTAVO H. G.. Hologram quantitative structure-activity relationship and comparative molecular interaction field analysis of aminothiazole and thiazolesulfonamide as reversible LSD1 inhibitors. Future Medicinal Chemistry, v. 7, n. 11, p. 1381-1394, 2015. (12/20990-2)

SILVA, G. N. S.; REZENDE, L. C. D.; EMERY, F. S.; GOSMANN, G.; GNOATTO, S. C. B.. Natural and Semi synthetic Antimalarial Compounds: Emphasis on the Terpene Class. MINI-REVIEWS IN MEDICINAL CHEMISTRY, v. 15, n. 10, p. 809-836, 2015. (12/20990-2)

FERREIRA, SAMUEL R. A.; FRANCO, MARCIA S. F.; DINIZ, EVELYN M. L. P.; EMERY, FLAVIO DA SILVA; CLOSOSKI, GIULIANO CESAR. Drug Likeness and Selective Functionalization of Quinoxalines. CURRENT ORGANIC SYNTHESIS, v. 12, n. 6, p. 714-729, 2015. (12/14362-9, 12/20990-2, 13/04766-8, 12/08589-0)

SANTOS, GABRIELA B.; GANESAN, A.; EMERY, FLAVIO S.. Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule. CHEMMEDCHEM, v. 11, n. 20, p. 2245-2251, OCT 19 2016. (12/20990-2)

FREIRE FRANCO, MARCIA SILVANA; DE PAULA, MURILO HELDER; GLOWACKA, PAULINA CECYLIA; FUMAGALLI, FERNANDO; CLOSOSKI, GIULIANO CESAR; EMERY, FLAVIO DA SILVA. Palladium-catalyzed C-H alkenylation of quinoxaline N-oxide enabled by a mono-N-protected amino acid. Tetrahedron Letters, v. 59, n. 26, p. 2562-2566, JUN 27 2018. (12/20990-2, 14/50265-3, 17/21146-4, 15/12811-9)

PAEZ GONZALEZ, MARIA TERESA; FUMAGALLI, FERNANDO; BENEVENUTO, CAROLINA GOMES; EMERY, FLAVIO DA SILVA; GASPAR, LORENA RIGO. Novel benzophenone-3 derivatives with promising potential as UV filters: Relationship between structure, photoprotective potential and phototoxicity. European Journal of Pharmaceutical Sciences, v. 101, p. 200-210, APR 1 2017. (12/20990-2, 10/00086-4)

Filed patent(s) as a result of this research project