title: Synthesis, antitumor screening and cell cycle analysis of novel benzothieno[3,2-b]pyran derivatives.
abstract: Three series of benzothiophene derivatives were designed and synthesized as cytotoxic agents. The compounds were subjected to in vitro antitumor screening at the National Cancer Institute (NCI), Bethesda, MD. The results of the single dose screening indicated that only the benzothieno[3,2-b]pyran series 3a-f exhibited potent and broad spectrum cytotoxic activity and was subjected to five dose cytotoxic screening. The most active compound in this study was 2-amino-6-bromo-4-(4-nitrophenyl)-4H-[1]benzothieno[3,2-b]pyran-3-carbonitrile (3e) with MG-MID GI50, TGI, and LC50values of 0.11, 7.94 and 42.66 μM, respectively. Compound 3e exhibited broad spectrum anticancer activity against a panel of 59 cell lines. To elucidate the underlying mechanism of compound 3e cytotoxic activity, we examined its effect on cell cycle progression and its ability to induce apoptosis using human colon adenocarcinoma cell line (HCT-116). The effect of compound 3e on the cell cycle progression indicated that exposure of HCT-116 cells to compound 3e for 24 and 48 h, induced a significant disruption in the cell cycle profile including time dependent decrease in cell population at G1 phase with concomitant increase in pre-G and G2/M cell population. Moreover, compound 3e induced time dependent increase in the percentage of early and late apoptotic and necrotic cell population. In conclusion, we were able to successfully design a new series of benzothieno[3,2-b]pyran derivatives with potent cytotoxic activity and their mechanism of cytotoxicity was examined.
authors: a Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors: Ashraf F
authors: AF
authors: Zaher
authors: a Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors: Suzan M
authors: SM
authors: Abuel-Maaty
authors: a Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors: Hala B
authors: HB
authors: El-Nassan
authors: b Department of Pathology, Molecular Pathology Unit , National Cancer Institute, Cairo University , Cairo , Egypt , and.
authors: Samir A S
authors: SA
authors: Amer
authors: c Department of Pharmacology and Toxicology, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt.
authors: Tamer M
authors: TM
authors: Abdelghany
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D013876:Thiophenes; C000614259:benzothieno(3,2-b)pyran
keywords: Antitumor activity; apoptosis; benzothieno[3,2-b]pyran; cell cycle analysis