Design, synthesis and biological evaluation of imidazopyridine–propenone conjugates as potent tubulin inhibitors
| Autor: | V. Lakshma Nayak, Ahmed Kamal, Ibrahim Bin Sayeed, Neeraj Kumar Chouhan, Mohd Adil Shareef |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Imidazopyridine Pharmaceutical Science 01 natural sciences Biochemistry Flow cytometry HeLa 03 medical and health sciences Annexin Drug Discovery medicine Pharmacology medicine.diagnostic_test biology 010405 organic chemistry Organic Chemistry Cell cycle biology.organism_classification Molecular biology 0104 chemical sciences Chemistry 030104 developmental biology Cell culture Apoptosis Molecular Medicine |
| Zdroj: | MedChemComm. 8:1000-1006 |
| ISSN: | 2040-2511 2040-2503 |
| Popis: | A library of imidazopyridine–propenone conjugates (8a–8u) were synthesized and evaluated for their antitumor activity against four human cancer cell lines, namely, prostate (DU-145), lung (A549), cervical (Hela) and breast (MCF-7) cancer cell lines. These conjugates showed good to moderate activity against the tested cell lines. Among them, two conjugates (8m and 8q) showed significant antiproliferative activity against the human lung cancer cell line (A549) with IC50 values of 0.86 μM and 0.93 μM, respectively. Flow cytometry analysis revealed that these compounds arrested the cell cycle at the G2/M phase in the human lung cancer cell line (A549), inhibiting tubulin polymerization leading to apoptosis. Further, Hoechst staining, decrease in mitochondrial membrane potential and Annexin V-FITC assay suggested that the cell death was due to apoptosis induction. Overall, the present investigation demonstrated that the synthesized imidazopyridine–propenone conjugates are promising tubulin inhibitors and apoptotic inducers. |
| Databáze: | OpenAIRE |
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