PHYTOCHEMICAL-BASED INHIBITION OF 5-ALPHA REDUCTASE TYPES I AND II: A COMPUTATIONAL METHOD FOR TREATING ANDROGENIC ALOPECIA

Abstract

Androgenic alopecia is a disorder affecting both males and females and causes progressive loss of hair, causing a person to become bald. Androgenic alopecia is caused by hyperactivity of the enzyme 5-alpha reductase, which causes it to metabolize more of the androgen testosterone. This increases the metabolism of testosterone, resulting in the formation of more dihydrotestosterone, which is a more potent androgen than testosterone. This dihydrotestosterone binds to the androgen receptors of hair follicles, causing a change in the shape of the receptor. This dihydrotestosterone binds to the androgen receptors of hair follicles, causing a change in the shape of the receptor. Due to this signalling pathway, the hair growth cycle is affected. As a result, the Anagen growth phase gets shortened and the Telogen phase gets longer. Due to the shortening of the Anagen phases, hair growth does not take place, and the follicles shrink, resulting in baldness. Currently, the FDA-approved drug Finasteride is used to treat androgenic alopecia, which inhibits the enzyme 5-alpha reductase and blocks the formation of dihydrotestosterone. But continuous use of Finasteride also shows side effects in the body, such as a decrease in libido, erectile dysfunction, etc. Hence, there is a need for a drug that has minimal side effects and is effective for androgenic alopecia. The two types of 5-alpha reductase, 5-alpha reductase type I and type II, are primarily responsible for androgenic alopecia. Hence, in this study, we inhibit both 5- alpha reductase type I and type II with the help of natural compounds. First of all, we obtain phytochemicals from different medicinal plants, later we do their molecular docking and ADMET analysis, and search for a drug-like compound. In this study, we found that the phytochemical Kaempferol obtained from Allium cepa shows higher binding affinity with both 5-alpha reductase enzymes than the control drug (Finasteride). The binding affinity of the phytochemical kaempferol with both 5-alpha reductases was found to be -9.2 kcal/mol. Moreover, this compound also follows all the ADME&T parameters, which makes it a better drug candidate.