On the Search for Potential Antimycobacterial Drugs: Synthesis of Naphthoquinoidal, Phenazinic and 1,2,3-Triazolic Compounds and Evaluation AgainstMycobacterium tuberculosis

Guilherme A. M. Jardim, Eduardo H. G. Cruz, Wagner O. Valença, Jarbas M. Resende, Bernardo L. Rodrigues, Daniela F. Ramos, Ronaldo N. Oliveira, Pedro E. A. Silva, Eufrânio N. da Silva Júnior
2015 Journal of the Brazilian Chemical Society  
Fifteen naphthoquinones, sixteen phenazines and fifteen aryl triazoles were synthesized and evaluated against Mycobacterium tuberculosis. Twenty five substances are reported here for the first time and, among all of the compounds evaluated, six presented MIC (minimal inhibitory concentration) values ≤ 6.25 μg mL -1 . These substances are promising antimycobacterial prototypes. 1,2,3-Triazoles are well known for their various biological activities, including anti-TB and antifungal activity, and
more » ... ngal activity, and these arise by inhibition of cell wall synthesis. 19 Recently, our group has devoted efforts to the preparation of new triazoles with potent biological activities, 15 including, for instance, β-lapachone and nor-β-lapachone-based 1,2,3-triazoles as potent trypanocidal compounds. 20, 21 In this context, as a continuation of our programme to develop new antimycobacterial compounds, we describe herein the synthesis of lapachone-based 1,2,3-triazoles and their respective phenazine derivatives, besides aryl triazoles. We also outline the evaluation these new derivatives against pan-susceptible M. tuberculosis H 37 Rv (ATCC 27294). -R = H (82%) 12 -R = Br (75%) 13 -R = F (78%) 14 -R = OMe (82%) 15 -R = Me (77%) 6 -R = H (65%) 7 -R = Br (59%) 8 -R = F (63%) 9 -R = OMe (67%) 10 -R = Me (55%)
doi:10.5935/0103-5053.20150067 fatcat:gz3zd2akdfhe7bogji5swigkzi