Synthesis and biological properties of a series of aryl alkyl disulfide derivatives

Disulfide containing compounds are recognized for their wide range of biological properties and are known for their important applications in the pharmaceutical field. In this study, a series of diaryl disulfides with varying alkyl chain length (C(8)-C(16)) was synthesized and assessed for their physicochemical and biological properties. The interactions of compounds with bovine serum albumin (BSA) was investigated in order to study their ability to bind with blood serum protein. An increase in the binding constants (K(a)) was observed with increasing chain length C(8)-C(12), while a decrease in value was obtained with compounds of chain length C(14) and C(16) showing a cut off effect at C(12). The thermodynamic parameters of binding indicated that the compounds bound to BSA mostly by van der Waals forces and hydrogen bonding. Molecular docking studies showed that the diaryl disulfides displayed greater binding affinity to Trp 213 rather than the Trp 134 residue on the BSA molecule. The trend observed in molecular docking is in line with the fluorescence binding studies whereby the C(12) derivative was found to show optimum affinity with BSA. The disulfide with chain length C(10) showed moderate antibacterial activity the highest inhibitory activity against Bacillus cereus. The cytotoxicity of the disulfides towards HaCaT cells decreased from C(8) to C(14). The overall results obtained show that these disulfides have potent antibacterial properties against Gram-positive bacteria Bacillus cereus at concentrations which are relatively non-toxic to normal cells.