[Final accepted version, unedited] Exploring the inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated quorum sensing utilizing QSAR and docking

Abstract

The world is under the great threat of antimicrobial resistance (AMR) leading to premature deaths. Micro-organisms can produce AMR via quorum sensing mechanisms utilizing S-adenocylhomocystiene/methiothioadenosine nucleosidase (SAH/MTAN) biosynthesis. But there is no specific drug developed till date to stop theSAH/MTAN which is a crucial target for the discovery of anti quorum sensing compound. It has been shown that the indazole compounds causes inhibition of SAH/MTA nucleosidase mediated quorum sensing, but the biochemical mechanisms have not yet been explored.Therefore, in this original research, an attempt has been made to explore essential structural features of these compounds by QSAR and molecular docking of indazole compounds having inhibition of SAH/MTA nucleosidase mediated quorum sensing. The validated QSAR predicted five essential descriptors and the molecular docking helps to identify the active binding amino acid residues involved in ligand receptor interaction are responsible for producing the quorum sensing inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated antimicrobial resistance.

Keywords

• Antimicrobial resistance
• Indazole compounds
• Quorum sensing
• QSAR
• Molecular docking
• SAH/MTA nucleosidase