Physicochemical Descriptors of Hydroxamic Acids used in Property Based Drug Design

Abstract

Hydroxamic acids (HAs) are key compounds in modern medicinal chemistry due to their ability to bind metal ions such as Fe(III) and Zn(II). Their role in inhibiting metalloenzymes like HDACs, CAs, MMPs, and ADAMs highlights their importance in drug development. Various synthetic methods have been developed to modify HAs with different functional groups, leading to bioisosteric derivatives with enhanced therapeutic potential. Molecular hybridization, wherein multiple pharmacophore groups are integrated into a single molecule, presents a promising approach to treat diseases by targeting multiple pathways simultaneously. This strategy could lead to effective treatments for cancer, infectious, and neurological diseases. The biological and pharmacological properties of HAs are significantly influenced by their metal-binding capability, with notable interactions with iron, zinc, magnesium, and calcium. Additionally, their physical properties, such as hydrogen bonding and lipophilicity (described by Log P), play a crucial role in drug design, influencing their biochemical interactions. Advances in protease inhibitor discovery, particularly those derived from HAs, further demonstrate their significance in therapeutic research. The unique behavior of HAs in solution, characterized by their molar volumes and interactions with solvents, underscores their versatile nature in drug formulation, with both hydrophilic and hydrophobic properties observed. newline