Synthesis of Amino Menthol derivatives for Enhanced Antimicrobial and Anti-inflammatory activity using In-silico Design

Abstract

The advent of multidrug-resistant bacteria has drawn attention to the need for innovative antimicrobials to treat life-threatening infections. The current study investigates the in-silico design and synthesis of new menthol derivatives to synthesize potent antibacterial and anti-inflammatory medicines. Menthol, a naturally occurring compound found in mint oils, has demonstrated various biological actions, like antimicrobial and anti-inflammatory properties. However, enhancing these activities through structural modification can lead to the development of more efficacious derivatives. The phenolic hydroxyl group of menthol was reacted with aromatic and aliphatic carboxylic acid in the presence of hydrochloric acid in dichloromethane to obtain novel derivatives of Menthol. In-silico design approaches such as molecular docking and computational chemistry were utilized to predict the binding affinity of the proposed menthol derivatives to important microbial and inflammatory targets. To optimize its interaction with target proteins, the menthol scaffold underwent key structural changes. The designed compounds were subjected to virtual screening against selected microbial targets, as well as anti-inflammatory targets, including cytokines and enzymes involved in inflammatory pathways. The results reveal promising interactions between the designed menthol derivatives and the selected targets, suggesting their potential as antimicrobial and anti-inflammatory agents. For antimicrobial activity (PDB ID: 4Q2W and PDB ID: 9LYZ) which demonstrated potential binding affinity between -6.9 to -7.3kcal/mol and -6.9kcal/mol to -7.6 kcal/mol respectively while compared with Gentamycin as a reference drug which showed binding affinity -6.2 kcal/mol and -6.7kcal/mol respectively and for anti-inflammatory activity PDB ID: 1CX2 demonstrated potential binding affinity between -9.2kcal/mol to -7.9 kcal/mol compared with Ibuprofen as reference drug which showed binding affinity -7.1kcal/mol. Furthermore, ADMET properties (Absorption, Distribution, Metabolism, Excretion and Toxicity) of the derived molecules had been anticipated to assess their drug-likeness and safety profiles. This in-silico method reveals insightful information about the possible medical uses of new menthol compounds. The proposed compounds require further experimental validation and synthesis to establish their biological properties and provide the path for the development of new antimicrobial and anti-inflammatory molecules derived from menthol.