Grinding and Microwave-assisted Synthesis of Heterocyclic Molecules in High Yields and Their Biological Evaluation

Abstract

Cis-cyclohexane1,2-dicarboxylic acid (1a), phthalic acid (1b), and pyrazine 2,3- dicarboxylic acid (1c) on grinding with hydrazine hydrate (2a) gave 2-aminohexahydro-1H-isoindole-1,3(2H)-dione (3a), 2-amino-1H-isoindole-1,3(2H)-dione (3b), and 6-amino-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione (3c), respectively. Condensation of (3a, 3b, 3c) with aldehydes (4x, 4y, 4z) and 2-cyanopyridine, 4-cyanopyridine, 2-cyanopyrazine (5x, 5y, 5z) under microwave irradiation gave corresponding azomethine (6ax, 6ay, 6az, 6bx, 6by, 6bz, 6cx, 6cy, 6cz) and amidine (7ax, 7ay, 7az, 7bx, 7by, 7bz, 7cx, 7cy, 7cz) derivatives, respectively. Fully characterized azomethine (6ax, 6ay, 6az, 6bx, 6by, 6bz, 6cx, 6cy, 6cz) and amidine (7ax, 7ay, 7az, 7bx, 7by, 7bz, 7cx, 7cy, 7cz) derivatives were screened for anti-inflammatory and anticancer activity against five human cancer cell lines. Compound 7cx exhibited 35% anti-inflammatory activity at a dose of 50 mg/kg p.o. whereas standard drug ibuprofen showed 39% activity at a dose of 50 mg/kg p.o. Compounds 6bz, 7cx, 7cz (breast T47D), 6bz, 6cy (lung NCI H-522), 6bx, 7bz (colon HCT-15), 6bz (ovary PA-1) and 6bx, and 6cz (liver HepG-2) exhibited good (35–41% inhibition at 10 ?M c) anticancer activity. IC50values of 6bx, 6bz, 6cy, 6cz, 7bz, 7cx, and 7cz against various cancer cell lines and normal cell (COS-1) are also reported. © 2015 HeteroCorporation