Debjani Banerjee

5-Nitrofuran-2-yl derivatives: Synthesis and inhibitory activities against growing and dormant mycobacterium species

Eighteen 5-nitrofuran-2-yl derivatives were prepared by reacting 5-nitro-2-furfural with various (sub)phenyl/pyridyl thiosemicarbazide using microwave irradiation. The compounds were tested for their in vitro activity against tubercular and various non-tubercular mycobacterium species in log-phase and 6-week-starved cultures. Compound N-(3,5-dibromopyridin-2-yl)-2-((5-nitrofuran-2-yl)methylene)hydrazinecarbothioamide (4r) was found to be the most potent compound (MIC: 0.22 microM) and was 3 times more active than standard isoniazid (INH) and equally active as rifampicin (RIF) in log-phase culture of Mycobacterium tuberculosis H37Rv. In starved M. tuberculosis H37Rv, 4r inhibited with MIC of 13.9 microM and was found to be 50 times more active than INH and slightly more active than RIF.

Efavirenz Mannich bases: Synthesis, anti-HIV and antitubercular activities

A series of efavirenz Mannich bases has been synthesized by reacting efavirenz, formaldehyde, and various aryl substituted piperazines using microwave irradiation (yield 35–88%). The synthesized compounds were evaluated for in-vitro anti-HIV and antimycobacterial activities. The in-vitro antiretroviral activities indicated that compound 7-(4-((6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2-oxo-2H-benzo[d] [1,3]oxazin-1 (4H)-yl)methyl)-3-methylpiperazin-l -yl)-1-cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (4i) was equipotent to efavirenz with EC50 of 2.4 nM. Compound 4i also inhibited M. tuberculosis with minimum inhibitory concentration of 0.2 μg/mL.

Synthesis and Antimycobacterial Evaluation of Novel Phthalazin‐4‐ylacetamides Against log‐ and Starved Phase Cultures

Twenty four novel 2‐[3‐(4‐bromo‐2‐fluorobenzyl)‐4‐oxo‐3,4‐dihydro‐1‐phthalazinyl]acetic acid amides were synthesized from phthalic anhydride and were subjected to in vitro and in vivo evaluation against log‐ and starved phase of mycobacterial species and Mycobacterium tuberculosis isocitrate lyase enzyme inhibition studies. Among the compounds screened, 2‐(2‐(4‐bromo‐2‐fluorobenzyl)‐1,2‐dihydro‐1‐oxophthalazin‐4‐yl)‐N‐(2,6‐dimethylphenyl)acetamide (5j) inhibited all eight mycobacterial species with MIC’s ranging from 0.08 to 5.05 μm and was non‐toxic to Vero cells till 126.43 μm. Four compounds were tested against starved culture of Mycobacterium tuberculosis and they inhibited with MIC’s ranging from 3.78 to 23.2 μm. Some compounds showed 40–66% inhibition against Mycobacterium tuberculosis isocitrate lyase enzyme at 10 μm. The docking studies also confirmed the binding potential of the compounds at the isocitrate lyase active site. In the in vivo animal model, 5j reduced the mycobacterial load in lung and spleen tissues with 1.38 and 2.9‐log10 protections, respectively, at 25 mg/kg body weight dose.

Discovery of novel antitubercular 2,10-dihydro-4aH-chromeno[3,2-c]pyridin-3-yl derivatives.

Twenty two novel 2,10-dihydro-4aH-chromeno[3,2-c]pyridin-3-yl derivatives were synthesized by reacting 3-formyl chromone, (sub)-2-amino pyridines, N1-(prop-2-ynyl)arylamides in the presence of indium triflate. The compounds were evaluated their preliminary in-vitro and in-vivo activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among them N-[(4aS)-2-(3-methyl-2-pyridinyl)-10-oxo-2,10-dihydro-4aH-chromeno[3,2-c]pyridin-3-yl]methyl-4-ethylbenzenecarboxamide 4d was found to be the most active compound in-vitro with MICs of 0.22 and 0.07 microg/mL against MTB and MDR-TB respectively. In the in-vivo animal model 4d decreased the bacterial load in lung and spleen tissues with 1.11 and 2.94-log10 protections respectively at 25 mg/kg body weight dose.

l-Proline-catalysed facile green protocol for the synthesis and antimycobacterial evaluation of [1,4]-thiazines

A series of ethyl 6-(4-chlorobenzoyl)-1,1-dioxo-3,5-diaryl-1,4-thiazinane-2-carboxylates was prepared in good yields (72-90%) from the reaction of ethyl 2-[(2-oxo-2-arylethyl)sulfonyl]acetate, substituted aromatic aldehydes and amines in presence of green catalyst, L-proline. These compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC(2)) using agar dilution method. Ethyl 6-(4-chlorobenzoyl)-3,5-di(4-nitrophenyl)-1,1-dioxo-1,4-thiazinane-2-carboxylate was found to be the most promising compound (MIC: 0.68 microM) active against MTB and MDR-TB.