Synthesis of novel 4,5-dihydropyrrolo[1,2-a]quinoxalines, pyrrolo[1,2-a]quinoxalin]-2-ones and their antituberculosis and anticancer activity.

A facile strategy was developed for the synthesis of biologically important 4,5-dihydropyrrolo[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 (NH3 SO3 ) 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.

Transition metal-free functionalized hydration of alkynes: one-pot synthesis of fluorinated ß-keto-imidates using Selectfluor.

A transition metal-free, four-component one-pot synthesis of polyfunctionalized fluorinated ß-keto-imidates via the functionalized hydration of alkynes has been described. The intermediate 1,3-ketoamino moiety was obtained from easily accessible arylpropioladehyde and arlyhydroxylamine and was treated with Selectfluor delivering fluorinated ß-keto-imidates. A wide variety of functional groups are tolerated under mild reaction conditions and the product applicability is highlighted.

Novel 1,3,4-oxadiazoles as antitubercular agents with limited activity against drug-resistant tuberculosis.

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.

Synthesis and evaluation of α-aminoacyl amides as antitubercular agents effective on drug resistant tuberculosis.

The development of an effective antitubercular agent is a challenge due to the complex nature of tuberculosis. Herein, we report the synthesis and evaluation of α-aminoacyl amides as antitubercular agents. The systematic medicinal chemistry approach led to identification of optimal substitutions required for the activity. Compound 11l was identified as antitubercular lead with drug like properties. Further, 11l selectively inhibited M. tuberculosis H37Rv with MIC value of 0.78 µM and was found to be non-toxic to CHOK1 cells. The lead compound inhibited multidrug resistant and Pre-Extensively drug resistant strains of Mycobacterium at 2 µg/mL and 8 µg/mL respectively.