Molecular docking and network pharmacology-based approaches to explore the potential of terpenoids for Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection is quickly countered by the host immune system; but, the pathogen is never eradicated. In this infection, 10% of infections are considered as open tuberculosis, while the remaining 90% are becoming latent, a state that can persist in the host for decades until immune control is lost. To date, more than 350 plant species have been studied in mycobacterial research. In this research, we used a mixture of software and database explorations to find the anti-mycobacterial possibilities of phytoconstituents. Maestro v12.7 and Cytoscape v3.8.0 were applied as software. In addition, the String v11.0, KEGG, Reactome and Pass Server databases assisted us in understanding TB cellular processes and phytoconstituent drug possibilities. The racemosol and pacharin have registered higher docking scores of 7.823 and -7.715 respectively. Furthermore, these compounds have substantial binding affinities in the active pocket of Mtb, and their docking metrics have consisted close to that of an approved drug (Rifampin). The network pharmacological exploration is also revealed possible connections with all of the TB-associated genes and other important signaling pathways. This computational study found that racemosol and pacharin were the safest anti-mycobacterial drugs for tuberculosis. Following comprehensive research of the pharmacological properties of racemosol and pacharin, we decided that this would be the first study to focus on anti-mycobacterial activity utilizing those compounds. Also, we believe that racemsosol and pacharin compounds will reveal potential actions when used in mycobacterial research. Furthermore, the derivatives of these compounds will be acted as possible drugs for tuberculosis and associated diseases. More pharmacological and toxicological explorations are required to have a better understanding of these compounds.