Head-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysis
| Autor: | Nizami Duran, Mehmet Abdullah Alagöz, Oztekin Algul, Ronak Haj Ersan, Serdar Burmaoglu, Tugba Ertan-Bolelli |
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| Rok vydání: | 2020 |
| Předmět: |
010405 organic chemistry
Chemistry In silico Organic Chemistry Antineoplastic Agents General Medicine 010402 general chemistry 01 natural sciences Small molecule Combinatorial chemistry Catalysis In vitro 0104 chemical sciences Inorganic Chemistry Bisbenzimidazole Cell culture Drug Discovery Antiproliferative Agents Cytotoxic T cell MTT assay Physical and Theoretical Chemistry Molecular Biology Information Systems |
| Zdroj: | Molecular diversity. 25(4) |
| ISSN: | 1573-501X |
| Popis: | In the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines. Among the various bisbenzazole derivatives, bisbenzoxazole derivatives exhibited the most promising anticancer activity followed by bisbenzimidazole and bisbenzothiazole derivatives. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in normal human cells, indicating selective and efficient antiproliferative activity of these bisbenzazole derivatives. The structure–activity relationships of heteroaromatic systems and linkers present in bisbenzazole derivatives were analyzed in detail. In silico ADMET prediction revealed that bisbenzazole is a drug-like small molecule with a favorable safety profile. Compound 31 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from methotrexate. Twenty-one bisbenzoxazole derivatives have been designed synthesized and evaluated to be an antiproliferative activity against four human tumor cell lines. |
| Databáze: | OpenAIRE |
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