In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives

Amila J Halahakoon

doi:10.12991/jrespharm.1695512

In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives

Abstract

Vinblastine was the first vinca alkaloid (VA) with antiproliferative properties discovered in the plant C. roseus. This study investigates the physicochemical and pharmacological properties of novel vinca derivatives, VADRPA01 and VADRPH01, compared to established vinca alkaloid drugs, including vincristine, vinblastine, vindesine, vinflunine, vinfosiltine, and vinorelbine. This study employs molecular docking and molecular dynamics simulations to investigate the inhibition of tubulin (PDB ID: 5J2T) self-assembly, with a focus on binding affinities and interaction profiles. Results indicate that vincristine, a first-generation alkaloid, exhibits the lowest binding affinity (-6.8 kcal/mol), associated with higher toxicity, while second- (vindesine, -7.4 kcal/mol) and third-generation (vinflunine, -11.1 kcal/mol) drugs demonstrate enhanced affinities. Key interactions, including hydrogen bonds, pi-pi, pi-alkyl, and pi-sigma bonds, were identified, with vinblastine forming robust hydrogen bonds with C:ASN329 and C:LYS336 (-10.8 kcal/mol) and vinorelbine engaging B:LYS176 and C:PHE351 (-10.7 kcal/mol). VADRPA01, a vinblastine derivative, exhibited superior binding affinity (-11.7 kcal/mol) and solubility (LogS7.4 -0.91), forming consistent hydrogen bonds with B:TYR210, C:ASN329, B:VAL177, and B:ASP179, with occupancy rates of 42.31% and 21.15% for B:TYR210 and C:VAL177/C:PHE351, respectively. Conversely, VADRPH01 lacked interaction with C:LYS326. Structural modifications, particularly in dihydrocatheranthine and N-formylvindoline moieties, significantly influenced docking conformations. The integration of docking, molecular dynamics, and gmxMMPB(GB)SA analyses underscores VADRPA01’s enhanced binding stability, positioning it as a promising antimitotic agent. These findings advocate for further development of VADRPA01, highlighting its potential in designing next-generation vinca alkaloids with improved therapeutic efficacy and safety profiles.

Keywords

Thanks

The author appreciates to Faculty of Computer Sciences, General Sir John Kotelawala Defence University, for providing the computer cluster for the analyses.

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Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Amila J Halahakoon ^*
0000-0002-4046-0859
Sri Lanka

Publication Date

March 15, 2026

Submission Date

May 9, 2025

Acceptance Date

December 21, 2025

Published in Issue

Year 2026 Volume: 30 Number: 2

DOI

https://doi.org/10.12991/jrespharm.1695512

IZ

https://izlik.org/JA56FB72XU

Cite

RIS / Bibtex

APA

Halahakoon, A. J. (2026). In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives. Journal of Research in Pharmacy, 30(2), 388-403. https://doi.org/10.12991/jrespharm.1695512

AMA

1.Halahakoon AJ. In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives. J. Res. Pharm. 2026;30(2):388-403. doi:10.12991/jrespharm.1695512

Chicago

Halahakoon, Amila J. 2026. “In Silico Analysis of Tubulin Self-Assembly Inhibition and Pharmaceutical Profiling of Novel Vinca Alkaloid Derivatives”. Journal of Research in Pharmacy 30 (2): 388-403. https://doi.org/10.12991/jrespharm.1695512.

EndNote

Halahakoon AJ (March 1, 2026) In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives. Journal of Research in Pharmacy 30 2 388–403.

IEEE

[1]A. J. Halahakoon, “In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives”, J. Res. Pharm., vol. 30, no. 2, pp. 388–403, Mar. 2026, doi: 10.12991/jrespharm.1695512.

ISNAD

Halahakoon, Amila J. “In Silico Analysis of Tubulin Self-Assembly Inhibition and Pharmaceutical Profiling of Novel Vinca Alkaloid Derivatives”. Journal of Research in Pharmacy 30/2 (March 1, 2026): 388-403. https://doi.org/10.12991/jrespharm.1695512.

JAMA

1.Halahakoon AJ. In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives. J. Res. Pharm. 2026;30:388–403.

MLA

Halahakoon, Amila J. “In Silico Analysis of Tubulin Self-Assembly Inhibition and Pharmaceutical Profiling of Novel Vinca Alkaloid Derivatives”. Journal of Research in Pharmacy, vol. 30, no. 2, Mar. 2026, pp. 388-03, doi:10.12991/jrespharm.1695512.

Vancouver

1.Amila J Halahakoon. In silico analysis of tubulin self-assembly inhibition and pharmaceutical profiling of novel vinca alkaloid derivatives. J. Res. Pharm. 2026 Mar. 1;30(2):388-403. doi:10.12991/jrespharm.1695512