In silico Assessment of Phytochemicals from Selected Plants as Prospective TGF‐β1 Inhibitors for Prostate Cancer Therapy

• Published in: ChemistrySelect (Weinheim) 2024-10, Vol.9 (40), p.n/a
• Main Authors: Ishabiyi, Felix Oluwasegun, Omotosho‐Sanni, Rukayat Yetunde, Baammi, Soukayna, Bourhia, Mohammed, Shazly, Gamal A., Ibenmoussa, Samir, Umar, Haruna Isiyaku
• Format: Article
• Language: English
• Subjects: In silico; Phytochemical; Plants; Prostate cancer; TGF‐β1
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202401413

Transforming growth factor β1 (TGF‐β) is a cytokine with pleiotropic biological functions. Recently, its signaling pathway has been highlighted for its implicative paradoxical roles in prostate cancer (PCa). Suppressing downstream effects of this pathway by interfering with receptor complex formation through inhibition of the TGF‐β1 leads to its antitumor effects, illuminating the TGF‐β1 as a viable therapeutic target for PCa. Our compound library—established by a literature‐based approach that identified phytochemicals with published evidence against the TGF‐β1—was screened by employing molecular docking, density functional theory (DFT), and molecular dynamic (MD) simulations to identify TGF‐β1 inhibitors. Eight of the 24 phytochemicals docked from our compound library had a good binding affinity (ranging from −11.7 to −10 kcal/mol) to the TGF‐β1 (PDB: 1PY5). The phytochemicals displayed good stability and reactivity as revealed by the DFT analysis and a desirable pharmacokinetic profile. The top four phytochemical complexes with high binding energies maintained stability throughout the 100  ns simulation. Qualitative studies on the drug repurposing attributes of bisindolylmaleimide, flavopiridol, baicalin, and gefitinib as inhibitors of TGF‐β1 are recommended; most importantly, suggest further wet‐lab studies to corroborate these phytochemicals—SB 202190, SB 203580, silymarin, and cryptotanshinone—in TGF‐β1 targeted drug development. TGF‐β1 has been indicated as a viable therapeutic target for prostate cancer therapy. Thus, we deployed structural bioinformatics tools to evaluate the therapeutic efficacy of phytochemicals, which have been documented to have inhibitory effects on this protein. Eight phytochemicals were identified and proposed for the treatment of prostate cancer.