| Autor: |
Dash SG; Centre of Excellence in Natural Products and Therapeutics, Department of Biotechnology and Bioinformatics, Sambalpur University, Sambalpur, Odisha, India., Suri C; Drug Discovery Research Centre, Translational Health Science and Technology Institute, Pali, Haryana, India., Nagireddy PKR; Fluoro and Agrochemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India., Kantevari S; Fluoro and Agrochemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India., Naik PK; Centre of Excellence in Natural Products and Therapeutics, Department of Biotechnology and Bioinformatics, Sambalpur University, Sambalpur, Odisha, India. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2021 Sep; Vol. 39 (14), pp. 5276-5289. Date of Electronic Publication: 2020 Jul 01. |
| DOI: |
10.1080/07391102.2020.1785945 |
| Abstrakt: |
Docetaxel (DOX) based combination therapy is a novel therapeutic strategy that attracts great interest in breast cancer treatment but its clinical utility got limited due to side effects. In contrast, noscapine, an antitussive drug showed antitumor activity against many cancers without any side effects that targets microtubules and attenuates its dynamic instability. In the quest for an increase in the anticancer activity of noscapine, we strategically designed a novel derivative, 9-vinyl phenyl noscapine (VPN), based on our in silico molecular docking and molecular dynamics simulation effort. Molecular docking of VPN and DOX onto microtubule revealed a docking score of -4.82 kcal/mol and -6.67 kcal/mol respectively, while the docking score of VPN was changed to -3.23 kcal/mol when it was docked onto the co-complex of tubulin-DOX. Further, the binding free energy (ΔG bind,PBSA ) of VPN and DOX with tubulin showed -24.04 and -18.65 kcal/mol respectively, while the binding free energy of DOX was increased further in combination with VPN (ΔG bind, PBSA was reduced to -21.41 kcal/mol), denoting combination effect of both ligands. The IC 50 value amounted to 30.17 µM and 19.92 µM for VPN and 0.621 µM and 0.193 µM for DOX, respectively for 48 h and 72 h. The dose dependent cytotoxicity of DOX has been reduced considerably with the combination dose regimen of VPN. Further, the combine effect of both the agents improved the apoptotic cell death 28.5% compared to single agent treatment 5.71% and 10.5% for VPN and DOX, respectively. Both agents bind effectively to tubulin in single and in combination to interfere with cell cycle progression in G2/M transition. This study provides novel concept of combination treatment of DOX and VPN to amend efficiency in breast cancer treatment.Communicated by Ramaswamy H. Sarma. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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