Biological evaluation and pharmacophore modeling of some benzoxazoles and their possible metabolites

• Published in: Archiv der Pharmazie (Weinheim) 2018-02, Vol.351 (2), p.n/a
• Main Authors: Zilifdar, Fatma, Foto, Egemen, Ertan‐Bolelli, Tugba, Aki‐Yalcin, Esin, Yalcin, Ismail, Diril, Nuran
• Format: Article
• Language: English
• Subjects: anticancer activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; benzoxazole; Benzoxazoles - chemistry; Benzoxazoles - metabolism; Benzoxazoles - pharmacology; Cancer; Cell Proliferation - drug effects; Cells, Cultured; comet assay; Cytotoxicity; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Metabolites; Models, Molecular; Molecular Structure; pharmacophore; SRB assay; Structure-Activity Relationship
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201700265

A series of benzoxazole derivatives and some possible primary metabolites were evaluated as anticancer agents. In vitro anti‐proliferative activities of the compounds were tested using the SRB assay on cancerous (HeLa) and non‐cancerous (L929) cell lines. It was found that 17 of 21 tested compounds had cytotoxic activity on HeLa cells and the cytotoxic activities of the compounds were 15–700 times higher than on L929 cells. We generated two distinct pharmacophore models for the cytotoxic activities of the compounds on HeLa and L929 cells. While active compounds such as camptothecin and X8 fitted the two models generated for both cell lines, selective cytotoxic compounds such as XT3B fitted only the model generated for HeLa cells. Evaluation of the genotoxic activities of the cytotoxic compounds with the alkaline comet assay revealed that compounds X17 and XT3 showed strong genotoxic effects against HeLa cells at low concentrations whereas they had no genotoxic effect on L929 cells. Due to the selective ability for inducing DNA strand breaks only on cancerous cells, the compounds were identified as effective derivatives for anticancer candidates. A series of benzoxazole derivatives and some possible primary metabolites were evaluated as anticancer agents. Of the 21 tested compounds, 17 showed 15–700 times higher cytotoxic activity on HeLa cells than on L929 cells. Two distinct pharmacophore models were generated for the cytotoxic activities of the compounds on HeLa and L929 cells, with active compounds fitting both models and selective compounds, such as XT3B, fitting only the model generated for HeLa cells.