Synthesis of novel 4,6-disubstituted quinazoline derivatives, their anti-inflammatory and anti-cancer activity (cytotoxic) against U937 leukemia cell lines.
In view of the link between use of NSAIDs and altered cancer incidence and a growing evidence of COX-II implication in angiogenesis, a novel series of 4,6-disubstituted quinazoline derivatives have been synthesized starting from anthranilic acid derivatives 1 through conventional methods. Initially acylation followed by cyclisation to obtain benz-oxazinones 2 which on further treatment with ammonia yielded the crucial intermediate, 2-substituted benzamide (3). The products were subsequently cyclised to obtain quinazolones 4, chlorinated 5, then hooked to various optically pure alpha-amino acids to have 4,6-disubstituted quinazoline derivatives 6. All the derivatives 6 are screened for anti-inflammatory and anti-cancer activity against U937 leukemia cell lines. Some of the compounds exhibited promising anti-cancer activity with reference to standard drug Etoposide.
Chandrika
P Mani
PM
Medicinal Chemistry Research Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal 506009, Andhrapradesh, India.
Yakaiah
T
T
Rao
A Raghu Ram
AR
Narsaiah
B
B
Reddy
N Chakra
NC
Sridhar
V
V
Rao
J Venkateshwara
JV
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D049109:Cell Proliferation / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D020298:U937 Cells / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D011799:Quinazolines; D002351:Carrageenan