Parallel synthesis, in vitro screening and SAR studies of a nitroderivatives compounds library active against macrophage's pathogens: Mycobacterium tuberculosis NRP forms and Leishmania sp

• Grant number: 13/01875-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: November 30, 2015
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Daniela Goncales Galasse Rando
• Grantee: Daniela Goncales Galasse Rando
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated researchers: Patricia Xander Batista

Abstract

Leishmaniasis is one the diseases that presents great social and economic importance around the world, being one of the 7 major parasitic diseases caused by protozoa. Tuberculosis emerges as a major challenge to the health departments reaching about a third of the world population and becoming epidemiologically significant because of the frequent co-infection with HIV. What these two diseases have in common? Both are classified by the World Health Organization as Neglected Diseases, since their pharmacological therapies are far from satisfactory, presents recognized toxicity, high cost and modest efficacy. Still, these diseases share another common characteristic: their etiological agents have, as host cell, the human macrophages. This proposal comes to reach the needs for developing new therapies for these diseases while gives continuity to the research carried out, since 2005, by the main researcher of this project. It is intended to enlarge, through parallel synthesis, a library of nitroderivatives which have already demonstrated significant in vitro activity against Leishmania donovani and Mycobacterium tuberculosis NRP forms, exploring molecular modifications in their chemical structures that generate greater diversity for studies of the structure-activity relationships. Finally, it is also expected to understand some of the toxicological behavior of these compounds comparing the effects over infected macrophages as well as on healthy cells. The most general objective of this project is to obtain relevant chemical and biological information for optimizing nitroderivatives with potential leishmanicidal and antimycobacterial NRP activities, which have also a suitable therapeutic profile for reaching the following stages of drug development: studies of chronic toxicity and pharmacology in vivo. (AU)

Scientific publications

(8)

(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)

LUIS OTÁVIO JUNQUEIRA; MARCELA OLIVEIRA LEGRAMANTI DA COSTA; DANIELA GONÇALES GALASSE RANDO. N-Myristoyltransferases as antileishmanial targets: a piggyback approach with benzoheterocyclic analogues. Brazilian Journal of Pharmaceutical Sciences, v. 55, 2019-10-24. (13/01875-0)

DA COSTA, MARCELA OLIVEIRA LEGRAMANTI; PAVANI, THAIS FERNANDA AMORIM; SCOTT, ANA LIGIA; RAMOS, DEBORA FELICIA VIEIRA; LAZARINI, MARIANA; RANDO, DANIELA GONCALES GALASSE. Nifuroxazide as JAK2 inhibitor: A binding mode proposal and Hel cell proliferation assay. European Journal of Pharmaceutical Sciences, v. 162, JUL 1 2021. (19/26686-2, 13/01875-0)

CORREA, MICHELLE FIDELIS; RAMOS BARBOSA, ALEFE JHONATAS; SATO, RIE; JUNQUEIRA, LUIS OTAVIO; POLITI, MARIO JOSE; RANDO, DANIELA GONCALES; DOS SANTOS FERNANDES, JOAO PAULO. Factorial design study to access the "green" iodocyclization reaction of 2-allylphenols. GREEN PROCESSING AND SYNTHESIS, v. 5, n. 2, p. 7-pg., 2016-04-01. (13/20479-9, 13/01875-0)

CORREA, MICHELLE FIDELIS; RAMOS BARBOSA, ALEFE JHONATAS; SATO, RIE; JUNQUEIRA, LUIS OTAVIO; POLITI, MARIO JOSE; RANDO, DANIELA GONCALES; DOS SANTOS FERNANDES, JOAO PAULO. Factorial design study to access the ``green{''} iodocyclization reaction of 2-allylphenols. GREEN PROCESSING AND SYNTHESIS, v. 5, n. 2, p. 145-151, APR 2016. (13/01875-0, 13/20479-9)

DE OLIVEIRA, DANIELA RODRIGUES; TODO, ANDREIA HATSUE; REGO, GIZELDA MAIA; CERUTTI, JANETE MARIA; CAVALHEIRO, ALBERTO JOSE; GALASSE RANDO, DANIELA GONCALES; CERUTTI, SUZETE MARIA. Flavones-bound in benzodiazepine site on GABA(A) receptor: Concomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin. European Journal of Pharmacology, v. 831, p. 77-86, JUL 15 2018. (09/15229-8, 13/01875-0)

ANDRE, FERNANDA R.; DOS SANTOS, PALOMA FREIRE; RANDO, DANIELA G.. Theoretical studies of the role of C-terminal cysteines in the process of S-nitrosylation of human Src kinases. Journal of Molecular Modeling, v. 22, n. 1, JAN 2016. (13/01875-0)

LOPES, ANDREY F. S.; SILVA, MARCOS P.. Schiff bases of 4-Phenyl-2-Aminothiazoles as hits to new antischistosomals: Synthesis, in vitro, in vivo and in silico studies. European Journal of Pharmaceutical Sciences, v. 150, JUL 1 2020. (13/01875-0)

RODRIGUES, CARINA AGOSTINHO; DOS SANTOS, PALOMA FREIRE; LEGRAMANTI DA COSTA, MARCELA OLIVEIRA; AMORIM PAVANI, THAIS FERNANDA; XANDER, PATRICIA; GERALDO, MARIANA MARQUES; MENGARDA, ANA; DE MORAES, JOSUE; GALASSE RANDO, DANIELA GONCALES. 4-Phenyl-1,3-thiazole-2-amines as scaffolds for new antileishmanial agents. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, SEP 10 2018. (13/01875-0)