XXI ALAM
Resumo:18-1


Prêmio
18-1ANTI-Mycobacterium tuberculosis ACTIVITY AND CYTOTOXICITY OF NEW FUROXAN DERIVATIVES COMPOUNDS
Autores:Souza Paula Carolina de (UNESP - Universidade Estadual Paulista- Campus de Araraquara- FCFar) ; Edmar Bonilla Gomes (UNESP - Universidade Estadual Paulista- Campus de Araraquara- FCFar) ; Heloisa Barbosa de Barros (UNESP - Universidade Estadual Paulista- Campus de Araraquara- FCFar) ; Clarice Queico Fujimura Leite (UNESP - Universidade Estadual Paulista- Campus de Araraquara- FCFar) ; Jean Leandro Santos (UNESP - Universidade Estadual Paulista- Campus de Araraquara- FCFar) ; Fernando Rogério Pavan (UNESP - Universidade Estadual Paulista- Campus de Araraquara- FCFar)

Resumo

Introduction: Tuberculosis ⟨TB⟩ is an infectious disease caused mainlyby Mycobacterium tuberculosis ⟨MTB⟩ and still an important public health problem worldwide. Factors like the emergence of multi-drug resistant strains ⟨MDR⟩ and resistance extended to drugs ⟨XDR⟩, makes urgent the search for new compounds as potential drugs.Furoxan derivatives has been described as pharmacophore subunit to be explore in Drug Design against infection diseases.Objective:In this work, we have determinated anti-MTB activity, cytotoxicity and selective index ⟨SI&rang of furoxan derivatives ⟨Lapdesf 1-5⟩ designed as new antitubercular drugs. Methods: The compounds Lapdesf 1-5 were previously synthesized by Laboratório de Pesquisa e Desenvolvimento de Fármacos - UNESP ⟨Lapdesf⟩. The Minimum Inhibitory Concentration ⟨MIC&rang was determined against MTB strain H37Rv ⟨ATCC 27294⟩ by using Resazurin Microtiter Assay ⟨REMA⟩ according to Palomino et al, 2002. The cytotoxicity index ⟨IC50⟩ on J774 macrophages lineage was determined through the methodology described by Pavan et al, 2010. In both trials, the results were observed by visual colorimetric change and fluorescence ⟨TECAN Spectrafluor®⟩ in response to cell metabolism. The SI was calculated by dividing IC50 by the MIC; if the SI is higher than 10, the compound was considered promising. Results and discussion: All compounds demonstrated antitubercular activity. The results observed were: Lapdesf1 ⟨MIC: 3,0µg⁄mL; IC50: 156,3µg⁄mL; SI: 52,1⟩;Lapdesf2 ⟨MIC 0,25µg⁄mL; IC50: 156,3µg⁄mL; SI: 625,2⟩;Lapdesf3 ⟨MIC: 0,4µg⁄mL; IC50:58,6µg⁄mL; SI: 146,5⟩; Lapdesf4 ⟨MIC: 4,31µg⁄mL; IC50: 78,1µg⁄mL; IS: 18,12⟩; Lapdesf5 ⟨MIC: 8,3µg⁄mL; IC50: 234,4µg⁄mL; SI: 28,24⟩. These results are comparable to the first line drugs ⟨MIC: EMB= 0,94-1,98 µg⁄mL; RFP= 0,05-0,20 µg⁄mL⟩. Conclusion: We identify a new prototype drug candidate compounds active against MTB. All compounds demonstrated antitubercular activity with SI higher than 10. These compounds are under current investigation and they will be further evaluated in vivo assays. Keywords:Mycobacterium tuberculosis; new drugs; furoxan. Financial support: CAPES and FAPESP ⟨proc.: 2009⁄06499-1 e 2011⁄11593-7⟩


Palavras-chave:  Mycobacterium tuberculosis, new drugs, furoxan