title: Synthesis and in vitro antitumor activity of new series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives.
abstract: New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives were synthesized and characterized by analytical and spectrometrical methods (IR, HRMS, (1)H and (13)C NMR). Nineteen of the synthesized compounds were selected by the National Cancer Institute (NCI), USA, to be screened for their antitumor activity at a single dose (10 μM) against a panel of 60 cancer cell lines. The most active compounds, 4, 6, 10, 14, 17 and 20 were selected for further evaluation at five dose level screening. Compounds 17 (GI50 = 0.44 μM, TGI = 1.2 μM and LC50 MG-MID = 6.6 μM) and 4 (GI50 = 0.77 μM, TGI = 2.08 μM and LC50 MG-MID = 11.74 μM) were proved to be the most active members in this study. 3D and 2D pharmacophoric maps for the structural features of both compounds were studied.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Moustafa T
authors.initials: MT
authors.lastname: Gabr
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: dr.nadiaelgohary@yahoo.com.
authors.forename: Nadia S
authors.initials: NS
authors.lastname: El-Gohary
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Eman R
authors.initials: ER
authors.lastname: El-Bendary
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: El-Kerdawy
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; C512478:EGFR protein, human; D066246:ErbB Receptors; C005465:benzothiazole
keywords: Antitumor activity; Benzothiazoles; Pharmacophore study; Pyrimidobenzothiazoles; Synthesis