Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates Journal Article
| Authors: | Marvania, B.; Lee, P. C.; Chaniyara, R.; Dong, H.; Suman, S.; Kakadiya, R.; Chou, T. C.; Lee, T. C.; Shah, A.; Su, T. L. |
| Article Title: | 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. © 2011 Elsevier B.V. All rights reserved. |
| Keywords: | controlled study; unclassified drug; human cell; dose response; drug dose reduction; drug efficacy; nonhuman; antineoplastic agent; mouse; cell cycle; unindexed drug; animal experiment; animal model; weight reduction; antineoplastic activity; cancer cell culture; drug structure; in vitro study; tumor xenograft; drug design; drug synthesis; structure activity relation; animalia; prostate cancer; cancer inhibition; breast carcinoma; cell cycle arrest; cell cycle g2 phase; cell cycle m phase; nitrogen mustards; drug cytotoxicity; drug dose increase; ic 50; dna cross linking; dna-directed alkylating agents; brassicaceae; anticancer agents; dna interstrand cross-linking agents; n (2 fluoro 3 chlorophenyl) 6 nitroquinazolin 4 amine; n (3 bromo 4 fluorophenyl) 6 nitroquinazolin 4 amine; n (3 bromophenyl) 6 nitroquinazolin 4 amine; n (3 chloro 4 fluorophenyl) 6 nitroquinazolin 4 amine; n (3 chloro 4 methoxyphenyl) 6 nitroquinazolin 4 amine; n (3 chlorophenyl) 6 nitroquinazolin 4 amine; n (3 ethynylphenyl) 6 nitroquinazolin 4 amine; n (3 fluorophenyl) 6 nitroquinazolin 4 amine; n (3 methoxyphenyl) 6 nitroquinazolin 4 amine; n (3,4 dichlorophenyl) 6 nitroquinazolin 4 amine; n (3,4,5 trimethoxyphenyl) 6 nitroquinazolin 4 amine; n (4 bromophenyl) 6 nitroquinazolin 4 amine; n (4 fluorophenyl) 6 nitroquinazolin 4 amine; n (4 phenoxyphenyl) 6 nitroquinazolin 4 amine; n [3 chloro 4 (pyridin 2 ylmethoxy)phenyl] 6 nitroquinazolin 4 amine; n [4 chloro 3 (trifluoromethyl)phenyl] 6 nitroquinazolin 4 amine; n' (2 cyano 4 nitrophenyl) n,n dimethylformimidamide; n4 (2 fluoro 3 chlorophenyl)quinazolin 4,6 diamine; n4 (2 fluoro 3 chlorphenyl)quinazolin 4,6 diamine; n4 (3 bromophenyl)quinazolin 4,6 diamine; n4 (3 chloro 4 fluorophenyl)quinazolin 4,6 diamine; n4 (3 chlorophenyl)quinazolin 4,6 diamine; n4 (3 fluoro 4 chlorophenyl)quinazolin 4,6 diamine; n4 (3 fluorophenyl)quinazolin 4,6 diamine; n4 (4 bromophenyl)quinazolin 4,6 diamine; n4 (4 fluorophenyl)quinazolin 4,6 diamine; n4 [ 3 (trifluoromethyl)phenyl]quinazolin 4,6 diamine; phenyl n mustard quinazoline conjugate |
| Journal Title: | Bioorganic & Medicinal Chemistry |
| Volume: | 19 |
| Issue: | 6 |
| ISSN: | 0968-0896 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2011-03-15 |
| Start Page: | 1987 |
| End Page: | 1998 |
| Language: | English |
| DOI: | 10.1016/j.bmc.2011.01.055 |
| PROVIDER: | scopus |
| PUBMED: | 21356592 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "CODEN: BMECE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work