Jitendra Kumar Mishra

Anti-tumor activity of a new series of benzoxazepine derivatives in breast cancer

A series of new benzoxazepine derivatives substituted with different alkoxy and aryloxy group were synthesized comprising synthetic steps of Mitsunobu reaction, lithium aluminum hydride (LAH) reduction, followed by debenzylation and finally intramolecular Mitsunobu cyclization. The new benzoxazepines specifically inhibited growth of breast cancer cell lines, MCF-7 and MDA-MB-231, but lack cytotoxicity to normal HEK-293 cells. The cell growth inhibition induced by the active compounds was due to cell cycle arrest at G(0)/G(1) phase. The active compound could cause significant reduction in tumor volume of MCF-7 xenograft tumor in nude mice model and their activity was comparable to that of tamoxifen citrate at 16mgkg(-1) dose at 30days of treatment. The identified most active compounds of the series have specific advantages as anti-cancer agent in breast cancer than tamoxifen.

Amino acid based enantiomerically pure 3-substituted benzofused heterocycles: A new class of antithrombotic agents

A diverse group of novel medium ring heterocycles derived from naturally abundant proteinogenic amino acids were evaluated for their potency towards antithrombotic activity. The more potent benzofused oxazepine and oxazocine scaffolds were diversified by incorporating different amino acids at the position number 3. Further the effect of ring size has also been taken into account and it was observed that the eight-membered oxazocines ane more potent compared to the corresponding oxazepines.

Studies toward a library of tetrahydrofurans: click and MCR products of mono- and bis-tetrahydrofurans.

Mono- and bis-tetrahydrofuran-based chemical libraries with diverse structural features have been prepared using the Sharpless azide-alkyne Click reaction and multi-component reactions (MCRs) such as Ugi and Biginelli reactions. Mono- and bis-tetrahydrofuran methyl azides, amines and ureas were key intermediates in these processes, and they were synthesized from the corresponding tetrahydrofuran methyl alcohols by mesylation followed by substitution with azide, reduction of the azide to the amine, and urea formation, as needed. Most mono- and tetrahydrofuran methyl alcohols were obtained by a Sharpless asymmetric dihydroxylation reaction. Alternatively, several mono-tetrahydrofurans were prepared by a cobalt(II) complex-catalyzed oxidative cyclization of bis-homoallylic alcohols, which were obtained by copper(I) iodide-catalyzed epoxide opening of 5,6-epoxyhex-1-ene with various alkyl and aryl Grignard reagents. These compounds are examples of an entirely new class of molecules in hitherto unknown chemical space, though their functions are yet to be determined presumably through random screening.