Preclinical prediction of phytochemicals identified from cannabis as novel inhibitors of TEX 11, DHCR24, and CatSper 1 in fertility drug design

Abstract

Medicinally, cannabis is gaining popularity and acceptance around the world despite public concerns regarding its legality. The wide range of phytochemical found in the Cannabis sativa (C. sativa) plant predisposes it to use in the treatment of a wide range of ailments or complications of existing diseases. The purpose of this study was to compare the efficacy of some reported phytochemicals in the hemp plant against three male fertility-associated proteins: testis expressed protein 11 (TEX 11), cation channel sperm associated 1 (CatSper 1), and 24-dehydrocholesterol reductase (DHCR24) with clomiphene, a selective estrogen receptor prescribed for infertility treatment, using computer-aided design. These proteins have been linked to varying degrees of oligospermia and are potential targets for drug development in the treatment regimen. The results of protein modeling, molecular docking, induced-fit docking simulation, ADME toxicity, and binding free energy for ligand-protein complexes revealed that the majority of compounds investigated demonstrated commendable binding affinity. When compared to the standard drug, clomiphene, the results for 5H-Naphtho[2,3-c] carbazole and cannabichromene were remarkably favorable in terms of free energy of binding and interaction with major amino acids. We believe that cannabichromene and 5H-naphtho[2,3-c]carbazole are both promising treatments and should be studied further for the treatment of male fertility disorders.

Keywords

• Phytochemicals
• Fertility
• In-silico
• 5H-Naphtho[2,3-c]carbazole
• Cannabichromene
• Molecular interaction