Deciphering the interaction of puerarin with cancer macromolecules: An in silico investigation

Abstract

The worldwide expanding increment in cancer pervasiveness is disturbing and this disease ranks among the main causes of mortality in both developing and developed countries. Unfortunately, available treatment options come with serious side effects and do not guarantee complete success. Although numerous models have been proposed for the development of better therapeutic agent, however the exact mechanism are still poorly understood. This then calls for continued research aimed at developing new drugs as an alternative or adjuvant anticancer agents. Here we have identified five vital proteins (CDK-2, Bcl-2, CDK-6, VEGFR, and IGF-1R) that aid tumor growth and we inhibited the activity of these proteins with Puerarin. Puerarin is an isoflavonoid C-glycosides used as a therapeutic agent against various human ailments. Our findings revealed that Puerarin fulfilled Veber’s rule. Added to this, CDK-6 and Bcl-2 had better glide scores for puerarin than the control (doxorubicin) and molecular simulation showed the stability of the complexes. These findings suggest that inhibiting CDK-6 and Bcl-2 with Puerarin could prove more effective in the management of cancer than doxorubicin. Overall, this study provides a new direction that could facilitate rational drug design for cancer.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cancer
• Puerarin
• CDK-6
• Bcl-2
• doxorubicin
• anti-cancer

Disclosure statement

No competing interests are declared by the authors.

Author’s contributions

A.O.F. R.T.A., T.A.A, and N.R.S. prepared, provided and analyzed the research data. R.T.A., T.A.A., N.R.S., and A.O.F. collected and analyzed the research data and contributed to the discussion. O.A.O., A.B.O., R.T.A., T.A.A., and A.O.F. wrote the draft manuscript and contributed to the discussion. O.A.O., A.B.O., A.O.F., N.R.S., B.O.A. B.E.O., and H.A.A designed the experiments and wrote, reviewed, and edited the manuscript. O.A.O. R.T.A., and A.O.F. guarantee this work, and, as such, had full access to all the information in the study and take responsibility for the precision of information and accuracy of data.

Data availability statement

Data are available on request.