title: Synthesis of some pyrazolines and pyrimidines derived from polymethoxy chalcones as anticancer and antimicrobial agents.
abstract: The synthesis of a series of certain polymethoxy chalcones and some derived pyrazole, pyrimidine, and thiazolopyrimidine ring structures is reported. Eleven compounds 4, 6, 9, 11, 14-17, 22, 24, and 25 were selected by the National Cancer Institute (NCI) to be screened for their in-vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in-vitro antimicrobial activity. Compounds 4, 6, and 11 were found to possess a significant broad spectrum antitumor potential against most of the tested subpanel tumor cell lines. The pyrazolines 4 and 6 displayed remarkable growth inhibitory activities (GI(50) MG-MID values of 2.10 and 1.38 µM, respectively), together with moderate cytostatic effects (TGI MG-MID values of 47.9 and 42.7 µM, respectively). Meanwhile, the pyrimidin-2-one 11 showed a noticeable overall tumor growth inhibitory activity, together with high cytostatic and cytotoxic efficacies (GI(50) , TGI and LC(50) MG-MID values of 3.39, 17.4, and 61.7 µM, respectively). On the other hand, compounds 3, 4, 13, 15, 19, 20, and 23 were found to be the most active antimicrobial members in this investigation with a broad spectrum of activity. Compound 23 was four times superior to ampicillin against Pseudomonas aeruginosa. The best antifungal activity was demonstrated by compounds 4, 5, and 11 which possessed almost half the activity of clotrimazole against Candida albicans. Collectively, the obtained biological results suggest that compound 4 could be considered as a possible dual antimicrobial-anticancer agent.
authors.affiliation: Department of Pharmaceutical Chemistry, King Abdulaziz University, Jeddah, Saudi Arabia. sherifrostom@yahoo.com
authors.forename: Sherif A F
authors.initials: SA
authors.lastname: Rostom
authors.forename: Mona H
authors.initials: MH
authors.lastname: Badr
authors.forename: Heba A
authors.initials: HA
authors.lastname: Abd El Razik
authors.forename: Hayam M A
authors.initials: HM
authors.lastname: Ashour
authors.forename: Abeer E
authors.initials: AE
authors.lastname: Abdel Wahab
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008826:Microbial Sensitivity Tests; D011720:Pyrazoles / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D047188:Chalcones; D011720:Pyrazoles; D011743:Pyrimidines