Aim: In recent times, heterocyclic chemotypes are being explored for the development of new antimycobacterials that target the drug-resistant tuberculosis. Here, we are disclosing the 5-substitued 2-mercapto-1,3,4-oxadiazoles as potent antitubercular agents. Methodology: A small library of 2-mercapto-1,3,4-oxadiazoles was synthesized using various acids. The compounds were evaluated for antituberculosis activity against M. tuberculosis H37Rv. Results: Compound 8j was identified as antitubercular lead with MIC of 0.6 μg/ml against M. tuberculosis H37Rv. This compound was nontoxic to CHO-K1 cells and showed selectivity index of 39. Of note, 8j showed antitubercular activity against pre-extensively drug-resistant clinical isolate of Mycobacterium with MIC of 2 μg/ml. Conclusion: This study provides potent antitubercular agent which can be further optimized to discover novel antibiotics.

No abstract

A facile strategy was developed for the synthesis of biologically important 4,5dihydropyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin]-2-ones by treating 2-(1H-pyrrol-1-yl)anilines with imidazo[1,2-a]pyridine-3-carbaldehyde or isatin, using amidosulfonic acid (NH 3 SO 3) as a solid catalyst in water at room temperature. The protocol has been extended to electrophile ninhydrin. The catalyst could be recycled for six times without the loss of activity. The compounds were evaluated for their antituberculosis, antibacterial, and anticancer activities. It is worth noting that compounds 3d and 3e demonstrated a minimum inhibitory concentration value of 6.25 µM against Mycobacterium tuberculosis H37Rv, whereas compounds 3d, 3g, 5d, 5e, and 5i showed a remarkable inhibition of A549, DU145, HeLa, HepG2, MCF-7, and B16-F10 cell lines, respectively. Staphylococcus aureus was inhibited by compounds 5b, 5e, 5d, 5g, and 5l at 32 µg/ml. K E Y W O R D S 4,5-dihydropyrrolo[1,2-a]quinoxalines, antituberculosis agents, pyrrolo[1,2-a]quinoxalin-2-ones, reusable catalyst 1 | INTRODUCTION Quinoxalines are nitrogen-containing heterocyclic compounds [1] exhibiting various biological activities, [2] acting as glucagon receptor antagonist, [3] inhibitors of human protein kinase CK2, [4] 5-HT 3 receptor agonist, [5] and gamma-aminobutyric acid receptor agonist. [6] Among these quinoxalines (Figure 1), 4,5-dihydropyrrolo[1,2-a]quinoxaline (1) is a key pharmacologically privileged scaffold exhibiting various activities including polycystic kidney disease inhibition. [7] The pyrrolo[1,2-a]quinoxaline derivative 2 showed an antipsychotic activity, [8] whereas 3 was found to be an adenosine A3 receptor modulator. [9] The pyrrolo[1,2-a]quinoxaline 4 has shown anti-HIV potential, [10] whereas 5 has been reported for its antiproliferative activity. [11] There are few reports on the synthesis of 4,5-dihydropyrrolo[1,2-a] quinoxalines and their spiro derivatives. [12] Preetham and Nath [13] reported the synthesis of pyrrolo-[1,2-a]quinoxalines and spiro derivatives using 2-(1H-pyrrol-1-yl)aniline with aldehyde or isatin or ketone in the presence of p-dodecylbenzenesulfonic acid catalyst in ethanol. Verma et al. [14] used 10 mol% AlCl 3 in tetrahydrofuran for the same transformation. In contrast, Zhou et al. [15] synthesized 12b-methyl-1,12bdihydrodipyrrolo[1,2-a:2′,1′-c]quinoxalin-3(2H)-one from 2-(1H-pyrrol-1yl)aniline and 4-pentynoic acid in the presence of Au(I) catalyst in water at 100°C. 14 Water Amidosulfonic acid 3 98 15 Water Amidosulfonic acid 4 98 Note: Reagents and conditions: 1a (0.088 mmol), 2a (0.088 mmol, 25 mg) in 2.0 ml of solvent at room temperature. Isolated yields (without column chromatography).