Informatics in Medicine Unlocked (Jan 2022)
Elucidating the interactions of bioactive compounds identified from Camellia Sinensis plant as promising candidates for the management of fibroids - A computational approach
Abstract
Uterine fibroids (UF), also known as uterine leiomyomas, uterine myomas, or fibromas, are benign monoclonal tumours and remain the most common gynaecological disorder in reproductive females. Although half of UFs affected women are asymptomatic and require no medical attention. However, the symptomatic require treatment that can be medicines, surgical techniques, and radiologically guided procedures. There has not been much progress in finding a medication that will entirely shrink or treat fibroid without causing severe side effects. Selective Progesterone Receptor Modulators (SPRMs) are a frequent therapeutic strategy in treating fibroids. Plants and their phytochemicals, for example, have been used to cure ailments and diseases for a long time. Because of their capacity to shrink tumours and decrease cell proliferation, Camellia Sinensis phytochemicals have the potential to be a successful treatment for uterine fibroids. This study investigated the inhibitory potentials of over 300 bioactive compounds from Camellia Sinensis by molecular docking analysis, pharmacophore modelling, and ADMET predictions against the progesterone receptor. Ethinyl estradiol, naringenin, apigenin, and (−)-epicatechin interacted with the receptor by forming hydrogen bonds with some essential amino acids at the receptor-binding site. These include GLN 725, ASN 719, CYS 891, and Pi-Pi stacking interactions with PHE 778, while naringenin, apigenin, and (−)-epicatechin have an additional hydrogen bond. (−)-Epiafzelechin, kaempferol, and tricetin produced hydrogen bonds and a Pi-Pi stacking interaction with GLN 725 and ASN 719. As a result, these molecular interactions may influence the structure and function of the protein. The pharmacophore models reveal chemical interactions that could explain the hit compounds' biological activity. ADMET analysis equally revealed that the compounds above met Lipinski's rule of five for orally delivered medicines with a low toxicity profile. As a result, these phytochemicals could be further studied to treat and manage uterine leiomyomas.
