Benzopyrazine (also known as quinoxaline) is a fused bicyclic heteroaromatic moiety that is found in many natural compounds, including commercial drugs. On the other hand, ultrasound irradiation is considered a primary green technique that substantially contributes to green synthesis. It is well-known that up-/downregulation of one or more specific enzyme(s) (proteins) is/are responsible for almost all diseases. Subsequently, appropriate inhibition of upregulating disease-causing enzyme(s) (direct or indirect) through enzyme-ligand interactions is considered an effective strategy for treating the specific disease. As a part of our ongoing research on new and greener methodology developments, we have synthesized a series of diversely substituted benzopyrazines under sonication without using any catalyst/support/additive/hazardous solvents. Our benzopyrazines were designed and in silico validated as trypanocidal and leishmanicidal agents. We carried out the in silico validation against Chagas’ disease and leishmaniasis (two major neglected tropical diseases) considering T. cruzi histidyl-tRNA synthetase (PDB ID: 4YPF) and T. cruzi trans-sialidase (PDB ID: 1S0J) as two major biological drug targets for Chagas’ disease whereas leishmanial rRNA A-site (PDB ID: 4K32) and leishmania major N-myristoyltransferase (PDB ID: 6QDA) as the major biomolecular drug targets for leishmaniasis. One of our benzopyrazines demonstrated comparable docking scores with two commercial drugs, miltefosine, and nifurtimox. Our newly developed methodology maintains atom economy and satisfies several aspects of green chemistry. The method as described herein may find its application in the future drug discovery process.

Ultrasound-assisted eco-friendly synthesis and in silico validation of benzopyrazines as trypanocidal/leishmanicidal agents

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.