In Silico Study of Newly Designed Tetracycline Derivatives for Its Antibiotic Activity

Tetracyclines are a vital class of antibiotics known for their broad-spectrum activity. However, the increasing emergence of tetracycline-resistant bacterial strains has posed significant therapeutic challenges. This study utilizes an in silico approach to design, evaluate, and optimize novel tetracycline derivatives with improved efficacy against TetR—a regulatory protein responsible for resistance. A total of 19 derivatives were subjected to ADMET screening, toxicity profiling, and molecular docking using PyRx, SwissADME, and Discovery Studio. Compounds C1, C11, C12, C14, C16, and C17 demonstrated superior binding affinity with ΔG values ranging from -7.7 to -8.9 kcal/mol. C1, with a fluorine substitution at the 7th position, exhibited the highest affinity. These molecules also fulfilled drug-likeness criteria and showed favorable safety profiles, suggesting potential as next-generation antibacterial agents. Further validation via molecular dynamics and biological assays is recommended.