Synthesis and evaluation of antiproliferative activity of novel quinazolin-4(3H)-one derivatives
| Autor: | Rajashaker Bantu, Nishant Jain, Suresh Kasaboina, Sridhara Janardhan, Lingaiah Nagarapu, Ramineni Venkatesh |
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| Rok vydání: | 2016 |
| Předmět: |
biology
010405 organic chemistry Stereochemistry Organic Chemistry Active site HDAC8 biology.organism_classification 01 natural sciences Combinatorial chemistry In vitro 0104 chemical sciences HeLa 010404 medicinal & biomolecular chemistry Piperazine chemistry.chemical_compound chemistry Docking (molecular) Cell culture biology.protein Mass spectrum General Pharmacology Toxicology and Pharmaceutics |
| Zdroj: | Medicinal Chemistry Research. 25:2070-2081 |
| ISSN: | 1554-8120 1054-2523 |
| Popis: | Two series of novel quinazolin-4(3H)-one derivatives (10a–g and 11a–g) have been synthesized and evaluated for their in vitro antiproliferative activity against human HeLa, MIAPACA, MDA-MB-231, and IMR-31 cancer cell lines. The synthesized compounds were characterized by spectral (Fourier transform infrared, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, high-resolution mass spectra) methods. Among them, compounds 11e and 11g exhibited potent in vitro antiproliferative activity with GI50 values 0.02, less than 0.01 μM against MIAPACA human cancer cell line. Significantly, compounds 10a, 10b, 10c, 10g, 11b, 11c, 11d, 11e, 11f showed activity with GI50 values ranging from 0.1 to 0.87 μM against human cancer cell lines MIAPACA, MDA-MB-231, and IMR-31. We have explored the probable binding mode and key active site interactions in HDAC8 and EHMT2 proteins. The docking results are complementary to the experimental results. |
| Databáze: | OpenAIRE |
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