UNVEILING THE POTENTIAL OF PHYTOCHEMICALS AGAINST LEPROSY AS AN ALTERNATIVE TO RIFAMPIN

Abstract

Leprosy is a chronic disease caused by Mycobacterium leprae and Mycobacterium lepromatosis that not only affects skin but also affects nervous system, internal organs and mucous membranes. It has remained a prevalent condition throughout history, that does not account for mortality but causes noticeable deformity which leads to lifelong stigma. Regardless of being designated "Eradicated" as a worldwide public health hazard by the WHO in 2017, it continues to exist around the world, primarily in Asia and Africa. In order to Treat leprosy WHO has advised a Multidrug regimen (Dapsone, Rifampin, Clofazimine) in 1982 and since then this regimen has remained the first line drug for treatment of leprosy. Rifampin is the most effective antibacterial medication used against leprosy. However, it has certain drawbacks, such as causing side effects such as liver dysfunction and thrombocytopenia, as well as inducing the activity of the metabolic enzyme Cyp3A4 in the liver and gut, resulting in a reduction in its half life as well as that of the drugs taken with it. To address this restriction of Rifampin, this research has conducted in which 35 phytocompounds were docked. Molecular docking is done against 3 different enzymes in order to get the alternatives of Rifampin which has the bactericidal effect along with Cyp3A4 inhibiting property. Docking is performed using the AutoDock Vina tool and Discovery Studio to determine the most efficient drug. Phytochemicals with the highest binding affinity are then chosen for further testing for toxicity, ADME (absorption, distribution, metabolism, and excretion), and drug-likeliness with the help of ProTox 3.0 and SwissADME web tools respectively. After all the analysis and screening only 5 phytochemicals are selected which can be used in place of Rifamycin, these are Tomatidine, Withaferin A, Glabrol, Glycyrrhetic Acid and Glabridin. These selected 5 compounds are shown to be less toxic and most effective comparative to Rifampin based on In-silico studies. However, in vivo investigations are required to gain confidence in the identified phytochemicals.