title: Synthesis, in vitro anticancer evaluation and in silico studies of novel imidazo[2,1-b]thiazole derivatives bearing pyrazole moieties.
abstract: A series of imidazo[2,1-b]thiazoles bearing pyrazole moieties 4-6(a-c) was synthesized through the reaction of 6-hydrazinylimidazo[2,1-b]thiazoles 3a-c with different β-dicarbonyl compounds. Eleven compounds were screened at the National Cancer Institute (NCI), USA for anticancer activity at a single dose (10 μM). The in vitro anticancer evaluation revealed that compounds 2a and 4-6(a) exhibited increased potency towards CNS SNB-75 and Renal UO-31 cancer cell lines. COMPARE analyses showed strong to considerable correlations with rapamycin (mTOR inhibitor). The results of assessment of toxicities, druglikeness, and drug score profiles of compounds 2a and 4-6(a) are promising. Some of the target compounds showed good docking scores with potential anticancer targets, chosen based on pharmacophore mapping of the established derivatives.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt. Electronic address: ahmed_reda551988@yahoo.com.
authors.forename: Ahmed R
authors.initials: AR
authors.lastname: Ali
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors.forename: Eman R
authors.initials: ER
authors.lastname: El-Bendary
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors.forename: Mariam A
authors.initials: MA
authors.lastname: Ghaly
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors.forename: Ihsan A
authors.initials: IA
authors.lastname: Shehata
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011720:Pyrazoles; D013844:Thiazoles; C031280:pyrazole
keywords: Aminothiazole; Anticancer evaluation; Imidazo[2,1-b]thiazole; In silico studies; Pyrazole