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The increase of incidence of tuberculosis (TB) with resistant strains and HIV co-infection has reinforced the necessity of developing new drugs for its treatment. The reaction of naphthoquinones with aromatic or aliphatic aldehydes in the presence of ammonium acetate led to the synthesis of the three β-lapachone derivatives (naphthoimidazoles) that were tested in this study. Phenazines were prepared by the reaction of the respective naphtoquinone with o-phenylenediamine in acetic acid under reflux. The antimicrobial activity of the derivatives was evaluated in vitro against Mycobacterium tuberculosis H37Rv (ATCC 27294) and the rifampicin-resistant strain (ATCC 35338) containing a His-526-Tir mutation in the rpoB gene. Using the Resazurin Microtiter Assay (REMA) method, bioactive molecules were observed in the susceptible and resistant strains with MICs ranging from 2.2 μM to 17 μM. The naphthoimidazoles with p-toluyl and indolyl group attached to the imidazole ring were more active against the H37Rv strain (MIC 9.12 μM and 4.2 μM, respectively) than the rifampicin-resistant strain (MIC 8.3 μM and 17 μM, respectively). The phenazine with the allyl-pyran group was most active among the two strains and had an MIC of 2.2 mM. These results show the potential of these molecules as prototypes for future drugs used in treating TB.

Genotyping tools have been widely used to study the occurrence of outbreaks and to identify the patterns of transmission of Mycobacterium tuberculosis strains. The clonal diversity of 65 clinical isolates of M. tuberculosis was determined by PCR methods. The Double Repeat Element method (DRE-PCR) and spoligotyping identified 45 and 26 distinct patterns respectively. Among these, LAM (38%) was the most frequent lineage, followed by Haarlem (31%) and T (20%). Five orphan patterns were not present in the SITVIT database. Mycobacterial interspersed repetitive units (MIRU) using 12 loci revealed 46 distinct patterns. MIRU loci 10, 23, 26 and 40 had the highest discriminatory power. The high genetic diversity found among M. tuberculosis isolates in this study suggests a high level of recent TB transmission, indicating an endemic mode of TB transmission and a putative importation of new TB genotypes. In addition, the high diversity among the isolates could indicate early detection of the infection in patients and an efficient rate of cure.