QSAR, molecular docking, MD simulations, and ADMET screening identify potential Heliotropium indicum leads against key targets in benign prostatic hyperplasia

Emmanuel Sunday Omirin; Precious Oluwasanmi Aribisala; Ezekiel Abiola Olugbogi; Olawole Yakubu Adeniran; Sunday Adeola Emaleku; John Ayodeji Saliu; Oluwaseun Fapohunda; Abimbola Kikelomo Omirin; Mary Oyinlola Gbadamosi; Iheanyichukwu Wopara

doi:10.1007/s40203-024-00280-7

QSAR, molecular docking, MD simulations, and ADMET screening identify potential Heliotropium indicum leads against key targets in benign prostatic hyperplasia

In Silico Pharmacol. 2024 Nov 19;12(2):107. doi: 10.1007/s40203-024-00280-7. eCollection 2024.

Affiliations

¹ Eureka Laboratory, Babcock University, Ilishan-Remo, Ogun State Nigeria.
² Department of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State Nigeria.
³ Department of Microbiology, Obafemi Awolowo University, Ife, Osun State Nigeria.
⁴ Department of Chemistry, Federal Polytechnic, Ado-Ekiti, Nigeria.
⁵ Department of Biochemistry, Federal University of Technology, Akure, Nigeria.
⁶ Department of Biochemistry, Rivers State University, Port Harcourt, Rivers State Nigeria.

PMID: 39569034
PMCID: PMC11573971 (available on 2025-11-19)
DOI: 10.1007/s40203-024-00280-7

Abstract

Steroid 5α-reductase (5αR) converts testosterone into dihydrotestosterone (DHT), a potent androgen driving prostate cell proliferation via the androgen receptor (AR). Both 5αR and AR play crucial roles in androgen-mediated disorders, making them key therapeutic targets in drug development. Current treatments target these enzymes individually and often cause significant side effects, highlighting the need for safer alternatives. Through in silico screening, 13 pyrrolizidine alkaloids of Heliotropium indicum (HI) were assessed for their inhibitory potential against 5αR and AR. Using machine learning, six alkaloids showed promising pIC50 values. The accuracy of the models was assessed using key statistical parameters, including the score, correlation coefficient for training sets (R²), correlation coefficient for test sets (Q²), standard deviation (SD), and root mean square error (RMSE). For 5αR, the results were 0.763 (R²), 0.781 (Q²), 0.748 (score), 0.362 (SD), and 0.832 (RMSE), while for AR, the values were 0.817 (R²), 0.783 (Q²), 0.713 (score), 0.427 (SD), and 0.782 (RMSE), indicating reliability. Europine-N-oxide (-10.27 kcal/mol) and Heliotridine-N-oxide (-9.72 kcal/mol) displayed stronger 5αR binding than Finasteride, while Heliotrine (-10.09 kcal/mol) and Europine-N-oxide (-8.76 kcal/mol) outperformed Enzalutamide in AR binding. Key hydrogen bonds and MD simulations confirmed stable interactions. Pharmacokinetic screening revealed favorable drug-like profiles, including good solubility and absorption with minimal CYP enzyme inhibition. These findings suggest that HI alkaloids are promising multi-target inhibitors for BPH treatment, warranting further in vivo validation and optimization.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-024-00280-7.

Keywords: 5AR and AR; Heliotropium indicum; In silico; MD Simulation; Machine learning; Pharmacokinetic.

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