Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Synthesis, Cytotoxicity and In Vitro Antileishmanial Activity of Naphthothiazoles

Full text
de Toledo, Juliano S. [1] ; Junior, Paulo E. S. [2] ; Manfrim, Viviane [2] ; Pinzan, Camila F. [1] ; de Araujo, Alexandre S. [3] ; Cruz, Angela K. [1] ; Emery, Flavio S. [2]
Total Authors: 7
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Univ Estadual Paulista, Dept Fis, Inst Biociencias Letras & Ciencias Exatas Sao Jos, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: CHEMICAL BIOLOGY & DRUG DESIGN; v. 81, n. 6, p. 749-756, JUN 2013.
Web of Science Citations: 4

The leishmaniasis is a spectral disease caused by the protozoan Leishmania spp., which threatens millions of people worldwide. Current treatments exhibit high toxicity, and there is no vaccine available. The need for new lead compounds with leishmanicidal activity is urgent. Considering that many lead leishmanicidal compounds contain a quinoidal scaffold and the thiazole heterocyclic ring is found in a number of antimicrobial drugs, we proposed a hybridization approach to generate a diverse set of semi-synthetic heterocycles with antileishmanial activity. We found that almost all synthesized compounds demonstrated potent activity against promastigotes of Leishmania (Viannia) braziliensis and reduced the survival index of Leishmania amastigotes in mammalian macrophages. Furthermore, the compounds were not cytotoxic to macrophages at fivefold higher concentrations than the EC50 for promastigotes. All molecules fulfilled Lipinski's Rule of Five, which predicts efficient orally absorption and permeation through biological membranes, the in silico pharmacokinetic profile confirmed these characteristics. The potent and selective activity of semi-synthetic naphthothiazoles against promastigotes and amastigotes reveals that the 2-amino-naphthothiazole ring may represent a scaffold for the design of compounds with leishmanicidal properties and encourage the development of drug formulation and new compounds for further studies in vivo. (AU)

FAPESP's process: 09/51812-0 - Development of a platform for the study of in vitro and in vivo metabolism of natural products, a need for pre-clinical testing system
Grantee:Norberto Peporine Lopes
Support type: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 09/14184-0 - Antiinfective compounds: bringing together medicinal chemistry and organic synthesis in search of lead antiparasitic compounds
Grantee:Flavio da Silva Emery
Support type: Regular Research Grants