title: Synthesis and Biological Evaluation of 2-Aminobenzothiazole and Benzimidazole Analogs Based on the Clathrodin Structure.
abstract: A series of 2-aminobenzothiazole and benzimidazole analogs based on the clathrodin scaffold was synthesized and investigated for their antimicrobial and antiproliferative activities as well as for their effects in hepatitis C virus (HCV) replicon model. Compound 7, derived from 2-aminobenzothiazole, exhibited moderate antimicrobial activity only against the Gram-positive bacterium, Enterococcus faecalis. In the antiviral assay, compounds 4d and 7 were found to suppress the HCV replicon by >70%, but also to exhibit cytotoxicity against the host cells (35 and 44%, respectively). Compounds 4a and 7 demonstrated good activity in the antiproliferative assays on the human melanoma cell line A-375. To assess the selectivity of the effects between cancerous and noncancerous cells, a mouse fibroblast cell line was used. The IC50 values for compound 7 against the melanoma cell line A-375 and the fibroblast cell line BALB/c 3T3 were 16 and 71 µM, respectively, yielding fourfold selectivity toward the cancer cell line. These results suggest that compound 7 should be studied further in order to fully explore its potential for drug development.
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Sofia
authors.initials: S
authors.lastname: Montalvão
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Teppo O
authors.initials: TO
authors.lastname: Leino
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Kiuru
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Katja-Emilia
authors.initials: KE
authors.lastname: Lillsunde
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.affiliation: Centre for Drug Research, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Tammela
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011758:Pyrroles / Q000737:chemistry*; D012093:Replicon; D013329:Structure-Activity Relationship
chemical_list: C000613237:(9H-fluoren-9-yl)methyl((2-aminobenzo(d)thiazol-6-yl)methyl)carbamate; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001562:Benzimidazoles; D052160:Benzothiazoles; D002219:Carbamates; D011758:Pyrroles; C077211:clathrodin
keywords: Antimicrobial activity; Antiproliferative assay; Cytotoxic activity; Synthesis