Chemical Profiling of Beta-Lactam and Derivatives for Antimicrobial Potential: A Computational Perspective

Abstract

Β-Lactam antibiotics play a pivotal role as essential antibacterial agents in modern medicine. However, the escalating threat of antibacterial resistance necessitates the development of novel antibacterial agents. In this study, we synthesized several β (Beta)-lactam derivatives with the aim of addressing these concerns. To address this concern, several β (Beta)-lactam derivatives were synthesized. The enzymatic targets for β-lactam antibiotics are the Binding Proteins (PBPs), responsible for the cell wall synthesis process. Molecular docking analyses were conducted with key PBP proteins, namely PBP2a, PBP2x, and SHV-1, to evaluate the potential of the synthesized β (Beta)-lactam derivatives. Notably, molecule 3b exhibited significant binding affinity based on Autodock Vina analysis among the three compounds studied—5-(Thiomorpholin-4-ylmethyl)- 1,3,4-oxadiazol-2(3H)-thione (3b),                4-Amino-2-[2-(5-amino-1,3,4-thiadiazol-2-yl)ethyl]-5- (morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazol-3-thione (6a), and 4-Amino-2-[2-(5-amino- 1,3,4-thiadiazol-2-yl)ethyl]-5-(thiomorpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazol-3-thione (6b). The conceptual framework involves the enzymatic targets, Binding Proteins (PBPs), and their interactions with key PBP proteins—PBP2a, PBP2x, and SHV-1—through molecular docking analyses. The hypothesis driving this research posits that the designed β (Beta)-lactam derivatives may exhibit enhanced antimicrobial properties. The research contributes to the development of effective antibacterial agents by unraveling the molecular interactions and stability of the synthesized compounds. Further validation through molecular docking simulations using the Desmond module from Schrödinger software, along with Molecular Dynamics (MD) simulations, revealed the stability of molecule 3b, as indicated by the Root Mean Square Deviation (RMSD) graph. This computational perspective provides valuable insights into the antimicrobial potential of β (Beta)-lactam derivatives, paving the way for the design and development of effective antibacterial agents in the face of increasing antibacterial resistance. The significance of this study lies in its contribution to the advancement of medical solutions in the context of evolving antibacterial resistance.