Synthesis and Structure−Activity Relationship of 2-Aminobenzophenone Derivatives as Antimitotic Agents

Abstract

A new type of inhibitor of tubulin polymerization was discovered on the basis of the combretastatin molecular skeleton. The lead compounds in this series, compounds 6 and 7, strongly inhibited tubulin polymerization in vitro and significantly arrested cells at the G(2)/M phase. Compounds 6 and 7 yielded 50- to 100-fold lower IC(50) values than did combretastatin A-4 against Colo 205, NUGC3, and HA22T human cancer cell lines as well as similar or greater growth inhibitory activities than did combretastain A-4 against DLD-1, HR, MCF-7, DU145, HONE-1, and MES-SA/DX5 human cancer cell lines. Structure-activity relationship information revealed that introduction of an amino group at the ortho position of the benzophenone ring plays an integral role for increased growth inhibition.

BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activityin Vivo

“…CA-4P (disodium combretastatin-A-4 -3-O-phosphate), a water-soluble prodrug, is a novel antitumor vascular targeting agent and is the first combretastatin analog to enter clinic trials (10,11). Our previous work showed that 2-aminobenzophenone types of CA-4 analogs exhibited strong cytotoxic activity against a wide variety of human cancer cells, including MDR-positive cancer cells (12).…”

High‐Efficiency Deep‐Blue Light‐Emitting Diodes Based on Phenylquinoline/Carbazole‐Based Compounds

“…3-Methoxy-2-aminobenzophenone (3) and 3-cyano-2-aminobenzophenone (4) were prepared as previously described. [18,19] 3-Acetyl-N-ethylcarbazole (1) was easily synthesized via a Friedel-Craft acylation reaction. Deep-blue emitting materials, PhQ-CVz, MeOPhQ-CVz, and CN-PhQ-CVz, were prepared by an acidcatalyzed Friedlander condensation reaction.…”

Antiangiogenic effect of 2-benzoyl–phenoxy acetamide in EAT cell is mediated by HIF-1α and down regulation of VEGF of in-vivo

“…The inhibitory role of benzophenone analogues against tumor growth is mediated through a direct effect on tumor cells that results in cell cycle arrest, differentiation, or apoptosis [28,29]. Combretastatin A-4, a benzophenone analogue exhibits a selective toxicity for proliferating endothelial cells in-vitro by induction of apoptosis and vascular shut down in human cancer models in-vivo [30]. Earlier we have reported the synthesis, in-vivo antitumor and proapoptotic activity of (2-aroyl-4-methylphenoxy) acetamides 4a-e, a benzophenone analogues [31].…”