| Área: Micobacteriologa ( Divisão C )
RESEARCH OF NEW MIXED-CHELATE COPPER COMPLEXES WITH QUINOXALINE AND ALANINE AS LIGANDS, POTENTIAL ANTIMYCOBACTERIAL AGENTS
Fernando Rogério Pavan (UNESP); Miriane Cristina Faradezo (UNIMED); Antonio J. Costa-filho (USP); Ernanni D. Vieira (USP); Antonio Monge (CIFA); Graciela Borthagaray (UDELAR); Dinorah Gambino (UDELAR); María H. Torre (UDELAR); Clarice Queico Fujimura Leite (UNESP)
Resumo
Introduction: Tuberculosis is an infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. It can lead to serious complications and even death, especially if it is accompanied by other bacterial infections and if the patients have their immune systems compromised by immunosuppressive drugs, abuse substances, or HIV/AIDS, among others. The World Health Organization (WHO) estimates that about 30 million people will be infected in the next 20 years, not only in the third world but also in the developed countries. In view of the importance of this disease and the emergence of multi-drug-resistant (MDR) strains, the investigation an development of new drugs is a leading area of research. The study of quinoxaline derivatives has become of much interest in recent years due to their antibacterial, antiviral, anticancer, antifungal, antihelminthes and insecticidal activities. Objetives: The present work describes the anti-M. tuberculosis activities of a new series of mixed-chelate Cu(II) complexes with different non- and mono-substituted 3-aminoquinoxaline-2-carbonitrile N1,N4-dioxide derivatives and alanine (ala) as ligands. Material and Methods: The MIC (Minimum Inhibitory Concentration) of three new complexes were investigated in order to determine their in vitro antimycobacterial activity against M. tuberculosis H37Rv (ATCC 27294). The MIC values were determined using the MABA method (Microplate Alamar Blue Assay). Results and Discussion: The MIC found for the three complexes were 7.8 ug/mL. The MIC values of all the complexes are of the same order than that of ethambutol (MIC = 5.62 ug/mL), an antimycobacterial agent in clinical use. Conclusion: Further studies should include the effect against drug-resistant strains and bacilli in a state of latency, as well as the intracellular evaluation of the new complexes.
Acknowledgements: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ref. Process: 2008/10390-2 and 2009/06499-1 and CYTED-RIIDFCM.
Palavras-chave: New Drugs, Anti-Mycobacterium tuberculosis, Copper Complexes, Quinoxaline, Alanina |