Discovery of β-carboline based Derivatives through Computational Aid for the Treatment of Leishmania

Abstract

Background:: Leishmaniasis is a phagocytic host cell invading, caused by leishmania species mostly found in developing nations. To treat leishmaniasis, a wide range of medications and potential vaccines are available, such as pentavalent antimonials, amphotericin, and miltefosined, but due to the lack of effective treatments, the high toxicity of chemotherapy and the growth of drug resistance linked to these diseases necessitate the urgent development of innovative therapeutic agents. β-carboline is a group of chemical compounds, and its derivatives have shown to be one of the potential candidates for the treatment of Leishmania. The carboline derivatives may have antileishmanial activity. Which act by interfering with the parasite’s DNA replication or metabolic processes, inhibiting the enzymes that are mainly responsible for the reproduction and metabolism of leishmania. Objective:: This research undertaking's present focus is on determining the existence and virtual screening of potential β-carboline derivative, which can act as an antileishmanial agent that can prevent or stop the progression of leishmania by the integration of different computational technologies such as in silico ADMET analysis and docking. Methods:: After synthesizing molecules using virtual screening, all designed compounds underwent molecular docking, and hit molecules underwent ADMET analysis. Results:: Using AutoDock Vina 1.5.6, molecular docking was carried out in the arginase receptor's active site (PDBID: 2AEB). The research and creation of compounds used virtual screening. Fifteen hits from docking experiments had high binding affinity as, in comparison to the commercially available molecule pentamidine (binding score -5.5Kcal/mol), 15 compounds (binding affinity - 7.9 to 7.0Kcal/mol). These Fifteen best hits were further examined for their ADME activity using SwissADME, and the ADME analysis identified 15 medicines as having the ideal ADME profile and improved bioavailability. Conclusion:: This research will bring up a broad spectrum of prospects for investigation into the disciplines of computational and medical research. This will facilitate the development of new antileishmanial agents that have better stability, bioavailability, and less toxicity, side effects for use in future research studies.