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

摘要

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-amino1H-isoindole-1,3(2H)-dione (3b), and 6-amino-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione (3c), respectively. Condensation of (3a-c) with aldehydes (4x-z) and 2-cyanopyridine, 4-cyanopyridine, 2-cyanopyrazine (5x-z) under microwave irradiation gave corresponding azomethine (6ax-cz) and amidine (7ax-cz) derivatives, respectively. Fully characterized azomethine (6ax-cz) and amidine (7ax-cz) 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 mu M c) anticancer activity. IC50 values of 6bx, 6bz, 6cy, 6cz, 7bz, 7cx, and 7cz against various cancer cell lines and normal cell (COS-1) are also reported.