title: Design, synthesis and biological evaluation studies of novel quinazoline derivatives as cytotoxic agents.
abstract: Some novel quinazoline derivatives 6a-h were designed, synthesized and evaluated for their in vitro cytotoxic activity against lymphoma cell line compared to etoposide as a reference drug. Compounds (S)-2-(6,8-diiodo-2-phenylquinazolin-4-ylamino)-3-phenylpropanoic acid (6 f), (S)-2-(6,8-diiodo-2-phenylquinazolin-4-ylamino)-3-(1H-imidazol-4-yl)propanoic acid (6 g) and (S)-2-(6,8-diiodo-2-phenylquinazolin-4-ylamino)-3-(1H-indol-3-yl) propanoic acid (6 h) had comparable higher cytotoxic activity than the reference drug. Compound 6 f, the most active compound, had IC50=13.2 µM. In an attempt to interpret such anti-cancer activity of these derivatives, their anti-inflammatory action was examined using the carrageenan induced rat paw edema method. The most active compounds showed moderate anti-inflammatory activity compared to the reference drug. In order to identify the most relevant physicochemical features important for high antitumor activity of the target compounds, specific 2D descriptors were calculated and correlated with the antileukemic activity.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah Al-munawarah, Kingdom of Saudi Arabia. Mohamad2zayed@yahoo.com
authors.forename: M F
authors.initials: MF
authors.lastname: Zayed
authors.forename: M H
authors.initials: MH
authors.lastname: Hassan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines