Structural analysis of ITS 1 gene of Leishmania tropica and evaluation of a novel ligand, benzo[d][1,3]dioxol-5-yl 4-acetamidobenzenesulfonate, via molecular modeling methods

Introduction Leishmaniasis, a prevalent tropical disease caused by intracellular protozoa of the genus Leishmania , poses significant health challenges globally, exacerbated by migration waves from endemic regions. Despite its widespread impact, an effective vaccine for leishmaniasis remains elusive. Historically, antimony compounds have been employed in its treatment, but the emergence of resistant strains necessitates the development of new therapeutic agents. Addressing this need, our study focused on the structural characterization of a previously uncharacterized protein from Leishmania tropica using computational biomolecular techniques. Methods We identified and docked the ligand benzo[d][1,3]dioxol-5-yl 4-acetamidobenzenesulfonate (3) and synthesized the reaction of sesamol (1) with sulfonyl chloride (2), and the NMR and IR spectra were used for characterization, a potential inhibitor of this protein, followed by a 300-ns simulation using the GROMACS software. Results The results showed that the protein structure in the ITS1 gene region of L. tropica consisting of 875 amino acids was effectively inhibited. In addition, based on the broad pharmacological properties of sesamol and sulfonate esters, as well as the results obtained from ProTox-III analysis, compound 3 was synthesized and its effect on L. tropica was investigated. This evaluation was further supported by DataWarrior, SwissADME, and ADMETlab analyses. The ligand’s moderate binding affinity (Δ G = −6.29 kcal/mol), the formation of multiple hydrogen bonds ( n = 4), its sustained binding throughout the 300-ns simulation, and the observed decrease in root mean square fluctuation (RMSF) values collectively support the idea that the synthesized compound may act as a potential inhibitor. Conclusion However, experimental studies are required to conclusively confirm its inhibitory efficacy. This study provides valuable insights for the development of new therapeutic approaches against leishmaniasis.