Inspection of in-house designed novel thiochromone amino-acid conjugate derivatives as Lm-NMT inhibitor – An in-silico analysis

Leishmaniasis is a complex neglected tropical disease caused by various leishmanial parasites that primarily affect the world's poorest people. A limited number of standard medications are available for this disease that has been used for several decades, which have drawbacks such as resistance, higher cost, and patient compliance, making it difficult to reach the poor. The search for novel chemical entities to treat leishmaniasis has led to target-based scaffold research. Thiochromone moieties in conjugation with aromatic amino acids have been considered for the study, along with possible substitutions of the electron-withdrawing and electron-donating groups. N-myristoyl transferase (NMT) has been selected as the molecular target for the study responsible for protein-protein interaction and ribosylation of proteins necessary for the growth inside the human body of the parasite. The designed novel thiochromone analogs were docked against the selected leishmanial NMT using thein-silico methods, physicochemical and toxicity properties were predicted, and Structure-Activity Relationship was also established in-silico. Finally, a molecular dynamics simulation study for 100 ns gave an idea about the stability of the protein-ligand complex. A time frame analysis of each 10 ns confirmation was also studied to understand better the putative binding pattern designed analogs. [Display omitted] •Leishmaniasis is a neglected tropical disease primarily affecting the world's poor population.•Thiochromone conjugates with aromatic amino acids were studied to target NMT.•In-silico docking of novel thiochromone analogs against leishmanial NMT.•Predicted physicochemical and toxicity properties and established Structure-Activity Relationship.•Molecular dynamics and time frame analysis of each 10 ns confirmation were also studied to better understand putative analogue binding patterns.