Virtual screening, SAR, and discovery of 5-(indole-3-yl)-2-[(2-nitrophenyl)amino] [1,3,4]-oxadiazole as a novel Bcl-2 inhibitor
| Autor: | Andrea Brancale, Malamati Kourti, Andrew D. Westwell, Alessandra Cavaliere, Arwyn Tomos Jones, Noha I. Ziedan, Filippo Prencipe, Rania Hamdy |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Indoles Stereochemistry Oxadiazole Antineoplastic Agents Enzyme-Linked Immunosorbent Assay Binding Competitive Biochemistry RS HeLa Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Drug Discovery Humans IC50 Cell Proliferation Pharmacology chemistry.chemical_classification Indole test Oxadiazoles Virtual screening Binding Sites biology Organic Chemistry biology.organism_classification Small molecule In vitro Protein Structure Tertiary Molecular Docking Simulation 030104 developmental biology Enzyme Proto-Oncogene Proteins c-bcl-2 chemistry Drug Design 030220 oncology & carcinogenesis Molecular Medicine HeLa Cells |
| Zdroj: | Chemical Biology & Drug Design. 90:147-155 |
| ISSN: | 1747-0277 |
| Popis: | A new series of oxadiazoles were designed to act as inhibitors of the anti-apoptotic Bcl-2\ud protein. Virtual screening led to the discovery of new hits that interact with Bcl-2 at the BH3\ud binding pocket. Further study of the structure-activity relationship of the most active\ud compound of the first series, compound 1, led to the discovery of a novel oxadiazole\ud analogue, compound 16j, that was a more potent small molecule inhibitor of Bcl-2. 16j had\ud good in vitro inhibitory activity with sub-micromolar IC50 values in a metastatic human\ud breast cancer cell line (MDA-MB-231) and a human cervical cancer cell line (HeLa). The\ud antitumour effect of 16j is concomitant with its ability to bind to Bcl-2 protein as shown by\ud an enzyme linked immunosorbent assay (IC50 = 4.27 μM). Compound 16j has a great\ud potential to develop into highly active anticancer agent. |
| Databáze: | OpenAIRE |
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