Synthetic aspects and biological activity profiles of hydrazone derivatives

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this paper provides valuable insights into the role of hydrazones as effective antimicrobial, anticancer and antioxidant agents. Their ease of synthesis through ester-hydrazide-hydrazone transformations allowed broad structural diversification, and several derivatives have shown low-to-mid micromolar activity supported by docking studies. Despite these advances, several challenges remain. First, most studies rely heavily on docking and cytotoxic assays without rigorous biochemical and cellular target validation. Second, data on selectivity indices and ADME/T properties are often limited. Third, structural and physiochemical issues such as E/Z isomerism, tautomerism, and stability are least overlooked, even though they may strongly influence biological outcomes. In addition, the lack of standardized assay protocols and reporting formats complicates direct comparison across studies. Addressing these gaps will require integration of structure-based design with orthogonal target validation methods, systematic selectivity and ADME/T profiling, and explicit investigation of isomerism and stability. Furthermore, the application of advanced biological models, such as patient-derived and in vivo efficacy studies, will be critical to bridge the gap between promising in vitro results and preclinical translation. By prioritizing these approaches, future work can enhance the reliability, reproducibility, and translational potential of hydrazone-based scaffolds, ultimately accelerating their progression from synthetic intermediates to viable therapeutic candidates.

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