title: Synthesis of new 2-substituted 6-bromo-3-methylthiazolo[3,2-alpha]-benzimidazole derivatives and their biological activities.
abstract: 1-(6-Bromo-3-methyl-1,3-thiazolo[3,2-alpha]benzimidazol-2-yl)ethanone (2) was prepared by bromination at ambient temperature of 1-(3-methylthiazolo[3,2-alpha]benzimidazol-2-yl)ethanone (1). The structure of 2 was determined by single-crystal X-ray diffraction. The precursor 5 was synthesized by heating a mixture of acetyl 2 and bromine. Various 2-substituted 6-bromo-3-methylthiazolo[3,2-alpha]benzimidazoles containing 1,3-thiazole, 1,4-benzothiazine, quinoxaline or imidazo[1,2-alpha]pyridine moieties were prepared starting from bromoacetyl 5. Taken together from the biological investigations, 2, 5, and 7a were potent immunosuppressors against both macrophages and T-lymphocytes, and 7b, 11b, and 14 were potent immunostimulators towards both types of immune cells. The results also revealed that, among others, 2 and 14 were the most significant inhibitors of LPS-stimulated NO generation, and that 5, 7a, and 7b had a weak radical scavenging activity against DPPH radicals. Moreover, 2, 5, and 7a had a concomitant strong cytotoxicity against colon carcinoma, hepatocellular carcinoma, and lymphoblastic leukemia cells. Collectively, compounds 2, 5, and 7a are multipotent compounds with promising biological activities.
authors.affiliation: Applied Organic Chemistry Department, National Research Center, Dokki 12622, Cairo, Egypt. hatem_741@yahoo.com
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.forename: Nehal A
authors.initials: NA
authors.lastname: Hamdy
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
authors.forename: Issa M I
authors.initials: IM
authors.lastname: Fakhr
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles