Graph Theoretical Network Analysis and Pharmacoinformatics-Based Investigation of Bioactive Compounds of Rasam (South Indian Recipe) Against Human Cancer

Abstract

Spice-rich recipes are referred to as "functional foods" because they include a variety of bioactive chemicals that have health-promoting properties in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in rasam (a south Indian cuisine) against oxidative stress-induced human malignancies. The rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase (MAPK)) and display their signaling route, a network was built. Among the identified compounds sixty-six bioactive compounds were used for in silico molecular docking study against MAPK, the top four compounds were chosen for further study based on their docking score and binding affinities. In silico predicted ADMET characteristics of the titled compounds were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology were also used to analyze the effectiveness and safety profile of top four selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK-ligand complex structure. Surprisingly, the discovered docking scores against MAPK revealed that the titled bioactive chemicals distribution varied between -3.5 and -10.6 kcal/mol. MD simulation validated the stability of four chemicals at the MAPK binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding affinity (-6.1 to -10.6 kcal/mol), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.