Design and synthesis of pyrazole–oxindole conjugates targeting tubulin polymerization as new anticancer agents
| Autor: | Ahmed Kamal, Anthony Addlagatta, Sumit S. Chourasiya, Rakesh Mishra, G. Bharath Kumar, Yerramsetty Suresh, Chandan Kishor, Anver Basha Shaik, Nishant Jain, Ananthamurthy Nagabhushana, Bhukya Supriya |
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| Rok vydání: | 2015 |
| Předmět: |
Indoles
Stereochemistry Antineoplastic Agents Pyrazole Microtubules Polymerization Structure-Activity Relationship chemistry.chemical_compound Tubulin Microtubule Drug Discovery Tumor Cells Cultured Animals Humans Oxindole Cytotoxicity Cyclin B1 Zebrafish Cell Proliferation Pharmacology Molecular Structure biology Organic Chemistry General Medicine Tubulin Modulators Oxindoles Molecular Docking Simulation chemistry Biochemistry Docking (molecular) Drug Design MCF-7 Cells biology.protein Pyrazoles Knoevenagel condensation Drug Screening Assays Antitumor HeLa Cells |
| Zdroj: | European Journal of Medicinal Chemistry. 92:501-513 |
| ISSN: | 0223-5234 |
| Popis: | A series of twenty one compounds with pyrazole and oxindole conjugates were synthesized by Knoevenagel condensation and investigated for their antiproliferative activity on different human cancer cell lines. The conjugates are comprised of a four ring scaffold; the structural isomers 12b and 12c possess chloro-substitution in the D ring. Among the congeners 12b, 12c, and 12d manifested significant cytotoxicity and inhibited tubulin assembly. Treatments with 12b, 12c and 12d resulted in accumulation of cells in G2/M phase, disruption of microtubule network, and increase in cyclin B1 protein. Zebrafish screening revealed that 12b, and 12d caused developmental defects. Docking analysis demonstrated that the congeners occupy the colchicine binding pocket of tubulin. |
| Databáze: | OpenAIRE |
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