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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Bhavin
authors.initials: B
authors.lastname: Marvania
authors.forename: Pei-Chih
authors.initials: PC
authors.lastname: Lee
authors.forename: Ravi
authors.initials: R
authors.lastname: Chaniyara
authors.forename: Huajin
authors.initials: H
authors.lastname: Dong
authors.forename: Sharda
authors.initials: S
authors.lastname: Suman
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kakadiya
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Su
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009149:Mustard Plant / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy; D011799:Quinazolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D014508:Urea