Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Determination of the anti-polo like kinase 1 potential of novel derivatives of thiophene using oncoinformatics approach

Moaath Khaled Aljbreen¹, Mohammed Mubarak Alrashidi¹, Amr Salah^2,3, Sibhghatulla Shaikh⁴, Syed Mohd Danish Rizvi5⁵

¹College of Pharmacy; ²Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, Kingdom of Saudi Arabia; ³National Organization for Drug Control & Research, Cairo, Egypt; ⁴Department of Medical Biotechnology, Yeungnam University, South Korea; ⁵Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail, Kingdom of Saudi Arabia.

For correspondence:- Syed Rizvi5 Email: syedrizvi10@yahoo.com

Accepted: 23 February 2021 Published: 31 March 2021

Citation: Aljbreen MK, Alrashidi MM, Salah A, Shaikh S, Rizvi5 SM. Determination of the anti-polo like kinase 1 potential of novel derivatives of thiophene using oncoinformatics approach. Trop J Pharm Res 2021; 20(3):505-510 doi: 10.4314/tjpr.v20i3.9

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To explore the anticancer mechanistic aspect of thiophene derivatives via targeting Polo like kinase 1 (PLK1).

Methods: The PLK1 enzyme is primarily expressed in cancer cells, and blocking its active site is one of the plausible ways to target cancer. Thus, in the present study, the thiophene derivatives were tested against PLK1 by molecular docking approach.

Results: Thiophene derivatives, named 8A, 8B and 14, exhibited better interactions with PLK1 active site than the positive control, doxorubicin. Molecular docking experiments revealed that 8A, 8B and 14 interacted efficiently with PLK1, and demonstrated binding energy and inhibition constant scores of ?-8.02 kcal/mol and 1.33 µM?, ?-8.65 kcal/mol and 0.454 µM? and ?-8.33 kcal/mol and 0.788 µM?, respectively. In contrast, doxorubicin-PLK1 interaction had binding energy of -7.95 kcal/mol and inhibition constant of 2.75 µM.

Conclusion: These results predict that thiophene derivatives 8A, 8B and 14 might exert anticancer effect by inhibiting PLK1 activity. Although, wet lab experiments are required to validate the data, however, these results may pave the way for the development of novel PLK1 inhibitors for anticancer therapy.

Keywords: Anticancer therapy, Cancer cells, Molecular docking, Polo-like kinase 1, Thiophene derivatives