Morusflavone, a New Therapeutic Candidate for Prostate Cancer by CYP17A1 Inhibition: Exhibited by Molecular Docking and Dynamics Simulation.

Sayed Aliul Hasan Abdi,Shabihul Fatma Sayed,Wasim Ahmad,Shatrunajay Shukla,Mohamed Jawed Ahsan,Amena Ali,Abuzer Ali,Abu Tahir

doi:10.3390/plants10091912

Sayed Aliul Hasan Abdi, Shabihul Fatma Sayed + Show 6 more

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https://doi.org/10.3390/plants10091912

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Abstract

Morusflavone, a flavonoid from Morus alba L., was evaluated for its interactive ability and stability with CYP17A1, in comparison with abiraterone, which is a Food and Drug Administration (FDA)-approved CYP17A1 inhibitor. CYP17A1 inhibition is an important therapeutic target for prostate cancer. The CHAMM36 force field was used to perform molecular dynamics (MD) simulations in this study. The results show that Morusflavone has significant interactive ability and stability for CYP17A1, in comparison with abiraterone. The final interaction energies for the Morusflavone–CYP17A1 and abiraterone–CYP17A1 complexes were −246.252 KJ/mol and −207.86 KJ/mol, respectively. Since there are only limited therapeutic agents available, such as abiraterone, galeterone, and seviteronel, which are being developed for prostate cancer, information on any potent natural anticancer compounds, such as vinca alkaloids, for prostate cancer treatment is limited. The results of this study show that CYP17A1 inhibition by Morusflavone could be an important therapeutic target for prostate cancer. Further preclinical and clinical evaluations of the lead compound Morusflavone are required to evaluate whether it can serve as a potential inhibitor of CYP17A1, which will be a new hope for prostate cancer treatment.

Highlights

Morus alba L. (Moraceae) known as a mulberry is a perennial, heterogeneous shrub
Molecular docking analysis was performed with Auto-Dock tools and 50 poses were generated as output
The results show that SASA of Morusflavone–CYP17A1 is similar to abiraterone–CYP17A1 (Figure 5)

Summary

Introduction

Morus alba L. (Moraceae) known as a mulberry is a perennial, heterogeneous shrub. Mulberry grows in a variety of climates, from tropical to sub-arctic [1,2]. The Morus alba L., plant contains various phytochemicals like alkaloids, flavonoids, glycosides, terpenoids, steroids, volatile oils, tannins etc. The majority of the constituents isolated from M. alba have been reported for their biological properties [3,4,5,6,7,8]. The cytotoxicity of M. alba or its isolated compounds has been tested on a variety of human cancer cells, including lung carcinoma, breast carcinoma, hepatocarcinoma, colorectal and cervical cancers [7,8,9,10,11]. Herbal constituents, such as Vinca alkaloids and S-allylcysteine, have been found to be useful for disease amelioration [10,12]

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