A new series of 2-phenol-4-aryl-6-chlorophenyl pyridine derivatives as dual topoisomerase I/II inhibitors: Synthesis, biological evaluation and 3D-QSAR study
| Autor: | Somin Shin, Kyu Yeon Jun, Youngjoo Kwon, Ganesh Bist, Tara Man Kadayat, Aarajana Shrestha, Til Bahadur Thapa Magar, Eung-Seok Lee, Radha Karki, Younghwa Na |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pyridines Stereochemistry Quantitative Structure-Activity Relationship Antineoplastic Agents HeLa 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Drug Discovery Humans Topoisomerase II Inhibitors Moiety Cytotoxicity Cell Proliferation Pharmacology Dose-Response Relationship Drug Molecular Structure biology Chemistry Topoisomerase Aryl Organic Chemistry Rational design General Medicine biology.organism_classification DNA Topoisomerases Type II 030104 developmental biology DNA Topoisomerases Type I 030220 oncology & carcinogenesis biology.protein Drug Screening Assays Antitumor Topoisomerase I Inhibitors Topoisomerase-II Inhibitor Terpyridine |
| Zdroj: | European Journal of Medicinal Chemistry. 113:228-245 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2016.02.050 |
| Popis: | As a continuous effort to develop novel antitumor agents, a new series of forty-five 2-phenol-4-aryl-6-chlorophenyl pyridine compounds were synthesized and evaluated for cytotoxicity against four different human cancer cell lines (DU145, HCT15, T47D, and HeLa), and topoisomerase I and II inhibitory activity. Several compounds (10-15, 20, 22, 24, 28, 42, and 49) displayed strong to moderate dual topoisomerase I and II inhibitory activity at 100 μM. It was observed that hydroxyl and chlorine moiety at meta or para position of phenyl ring is favorable for dual topoisomerase inhibitory activity and cytotoxicity. Most of the compounds displayed stronger cytotoxicities than those of all positive controls against the HCT15 and T47D cell lines. For investigation of the structure-activity relationships, a 3D-QSAR analysis using the method of comparative molecular field analysis (CoMFA) was performed. The generated 3D contour maps can be used for further rational design of novel terpyridine derivatives as highly selective and potent cytotoxic agents. |
| Databáze: | OpenAIRE |
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