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ORIGINAL RESEARCH article

Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 12 - 2024 | doi: 10.3389/fchem.2024.1418975
This article is part of the Research Topic Beyond Borders: Exploring Diverse Roles of Heterocyclic Compounds in Combatting Infections and Cancer View all 4 articles

Exploring Novel Apalutamide Analogues as Potential Therapeutics for Prostate Cancer: Design, Molecular Docking Investigations and Molecular Dynamics Simulation

Provisionally accepted
Ajay K. Gupta Ajay K. Gupta Yogesh Vaishnav Yogesh Vaishnav Sanmati K. Jain Sanmati K. Jain *
  • Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India

The final, formatted version of the article will be published soon.

    Prostate cancer (PC) ranks as the second most frequent type of cancer in men and is the fourth largest cause of mortality worldwide. Androgenic hormones such as testosterone and dihydrotestosterone are crucial for the development and progression of the prostate gland. Androgenic hormones bind to androgen receptors (AR) and trigger the synthesis of many genes that stimulate the growth of prostate cells, initiating PC growth. Apalutamide (APL) is a non-steroidal antiandrogen drug used to treat PC; however, it also causes a variety of toxicities and resistance during the treatment. The purpose of this study was to computationally identify new and safer analogues of APL, focusing on improved pharmacokinetic properties and reduced toxicity. Drug likeness (DL) and drug score (DS) were also calculated. Docking studies on the designed analogues were conducted to predict their binding affinities and compare their orientations with the ligands in the original crystal structure. We generated a total of 1415 analogues for different groups of APL using the bioisosteric approach. We selected 80 bioisosteres based on pharmacokinetic profiles and DL and DS score predictions and found that the designed APL bioisosteres were optimal to good compared to APL. Analogues APL19, APL35, APL43, APL76, and APL80, formed hydrogen bonds with protein (PDB ID: 5T8E) which is similar hydrogen bonding to the standard (APL). The MD simulation result confirmed that APL43 and APL80 complexes were stable during the 100 nS run. The results suggest that the APL analogues, particularly APL43 and APL80, are predicted to be potential antiandrogen drugs for the treatment of prostate cancer.

    Keywords: Apalutamide, prostate cancer, bioisosteric approach, Molecular Dynamics Simulation, molecular docking 1

    Received: 17 Apr 2024; Accepted: 04 Jul 2024.

    Copyright: © 2024 Gupta, Vaishnav and Jain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sanmati K. Jain, Guru Ghasidas Vishwavidyalaya, Bilaspur, 495 009, Chhattisgarh, India

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