Abstract

IN SILICO MOLECULAR DOCKING, DRUG-LIKENESS AND ADMET STUDIES OF QUINAZOLINE DERIVATIVES AGAINST PTR1 ENZYME (PDB ID: 1E7W) FOR ANTILEISHMANIAL ACTIVITY

Mr. Rahul Meena*, Mr. Shashank Saxena, Ms. Ghazala Qureshi, Mr. Mr. Ashish Khandvi, Ms. Muskan Soni, Mr. Jeevan Singh Bodana

Abstract

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania, posing a significant global health burden. The emergence of drug resistance and the limitations of current therapeutic agents necessitate the discovery of novel antileishmanial compounds. In the present study, an in silico approach was employed to evaluate the antileishmanial potential of selected quinazoline derivatives targeting Pteridine Reductase 1 (PTR1), a key enzyme involved in the parasite's folate metabolism pathway. The three-dimensional crystal structure of PTR1 (PDB ID: 1E7W) was obtained from the Protein Data Bank and used for molecular docking studies. A series of quinazoline derivatives were designed and docked into the active site of PTR1 using molecular docking software to investigate their binding affinity and interaction patterns. The docking results revealed that several derivatives exhibited favorable binding energies and formed stable interactions with crucial active-site amino acid residues, suggesting strong inhibitory potential against PTR1. Furthermore, drug-likeness properties were evaluated based on Lipinski’s Rule of Five, indicating that the majority of the compounds possessed desirable physicochemical characteristics for oral bioavailability. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis was performed to assess pharmacokinetic behavior and safety profiles. The selected lead compounds demonstrated acceptable ADMET parameters, including good intestinal absorption, low toxicity risk, and favorable pharmacokinetic properties. Overall, the findings suggest that quinazoline derivatives may serve as promising lead molecules for the development of novel antileishmanial agents targeting PTR1. Further in vitro and in vivo investigations are recommended to validate their therapeutic efficacy and safety.

Keywords: Leishmaniasis, Quinazoline Derivatives, Pteridine Reductase 1 (PTR1), Molecular Docking, Drug-Likeness, ADMET, In Silico Studies, Antileishmanial Activity.