Click chemistry-assisted synthesis of triazolo linked podophyllotoxin conjugates as tubulin polymerization inhibitors
| Autor: | Ahmed Kamal, V. Saidi Reddy, Abdullah Alarifi, V. Lakshma Nayak, Ibrahim Bin Sayeed, Kunta Chandrasekhar, M.V.P.S. Vishnuvardhan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Pharmaceutical Science 01 natural sciences Biochemistry HeLa 03 medical and health sciences Drug Discovery otorhinolaryngologic diseases medicine Pharmacology biology 010405 organic chemistry Chemistry Organic Chemistry biology.organism_classification Molecular biology 0104 chemical sciences 030104 developmental biology Tubulin Podophyllotoxin Docking (molecular) Apoptosis Cell culture Click chemistry biology.protein Molecular Medicine medicine.drug |
| Zdroj: | MedChemComm. 8:1817-1823 |
| ISSN: | 2040-2511 2040-2503 |
| Popis: | A series of new triazolo linked 4β-amidopodophyllotoxin conjugates (9a-l) were synthesized using click chemistry and evaluated for their antitumor activity against four human cancer cell lines. Among them, two compounds (9c and 9j) showed significant anticancer activity with IC50 values of 0.9 and 0.07 μM, respectively. Biological studies are conducted into the cell-cycle distribution of these conjugates inducing G2/M-phase arrest, apart from an increase in the levels of caspase-3 proteins, followed by apoptotic cell death. A tubulin polymerization assay analysis showed that these compounds effectively inhibit microtubule assembly in HeLa cells and, moreover, Hoechst 33258 and Immunohistochemistry staining suggest that these compounds induce cell death by apoptosis. The docking studies showed that compounds 9c and 9j interact and bind efficiently with the tubulin protein at the colchicine site. |
| Databáze: | OpenAIRE |
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