Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates.

Abstract

A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety. The preliminary antitumor studies revealed that these agents exhibited significant antitumor activity in inhibiting various human tumor cell growths in vitro. Compounds 21b, 21g, and 21h were selected for further antitumor activity evaluation against human breast carcinoma MX-1 and prostate PC-3 xenograft in animal model. These agents showed 54-75% tumor suppression with low toxicity (5-7% body-weight changes). We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase.

• Authors: Bhavin Marvania, Pei-Chih Lee, Ravi Chaniyara, Huajin Dong, Sharda Suman, Rajesh Kakadiya, Ting-Chao Chou, Te-Chang Lee, Anamik Shah, Tsann-Long Su
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 19 Issue 6 Pg. 1987-98 (Mar 15 2011) ISSN: 1464-3391 [Electronic] England
• PMID: 21356592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Quinazolines
• Urea

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, therapeutic use, toxicity)
• Cell Line, Tumor
• Drug Design
• Humans
• Mice
• Mice, Nude
• Mustard Plant (chemistry)
• Neoplasms (drug therapy)
• Quinazolines (chemistry)
• Structure-Activity Relationship
• Urea (chemistry)
• Xenograft Model Antitumor Assays