In Silico Studies Molecular Docking on Benzimidazole And Triazole, Toxicity and Qsar

The relentless emergence of drug-resistant microbial strains has intensified the global search for novel therapeutic agents with enhanced efficacy and safety profiles. In this context, the benzimidazole and triazole scaffolds have garnered significant attention due to their broad-spectrum biological activities, particularly their antimicrobial and anticancer properties. This study explores the potential of newly designed benzimidazole and triazole derivatives through in silico molecular docking methodologies to identify promising leads for drug development. The study focused on computational docking of designed compounds with two key biological targets: DNA gyrase (PDB ID: 6RKS) and human topoisomerase II (PDB ID: 1ZXM), enzymes crucial to DNA replication and cell proliferation, and known to be validated targets in antimicrobial and anticancer drug discovery. Molecular docking was performed using Autodock 4.2, and the docking results were evaluated based on binding affinity, hydrogen bond interactions, and overall binding pose stability within the active site of the target proteins. The benzimidazole and triazole derivatives demonstrated significant binding affinity toward both target proteins. Among the designed compounds, several ligands exhibited binding energies surpassing those of standard reference drugs such as ciprofloxacin and etoposide. In particular, compounds with electron-withdrawing substituents and heterocyclic moieties at strategic positions of the benzimidazole and triazole rings showed improved interaction profiles. These favorable interactions included multiple hydrogen bonds and hydrophobic contacts, indicating strong and specific binding within the enzymatic active sites.Furthermore, the pharmacokinetic properties and drug-likeness of the ligands were evaluated using Lipinski’s Rule of Five and ADMET predictions, confirming the acceptable oral bioavailability and low toxicity of the top-scoring compounds. The in-silico findings suggest that the synthesized molecules have the potential to act as dual inhibitors of microbial and human topoisomerases, presenting a unique avenue for the development of multifunctional therapeutic agents. This study highlights the utility of molecular docking as a powerful predictive tool in the early phases of drug discovery. By integrating structural chemistry with computational biology, it is possible to efficiently screen and optimize novel scaffolds prior to in vitro and in vivo evaluations. The promising docking results of benzimidazole and triazole derivatives underscore their potential as future leads for the development of antimicrobial and anticancer drugs, warranting further experimental validation.