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

Abstract

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.

Synthesis, Characterization and Antibacterial Assays of Novel N,N1‐Disubstituted 2,2′‐Dithiodianiline Derivatives

“…Interestingly, the 2,2'-dithiodianiline itself demonstrated in vitro antibacterial properties against multidrug resistant Acinetobacter baumannii. [37] Incorporation of a long-chains of NHCOC 9 H 20 [32] and NHCOC 11 H 23 [38] on its phenyl provided the compounds with antibacterial efficacy against Bacillus cereus, [39] whereas the including of Schiff base structures resulted in compounds with anti-Klebsiella pneumonia, [39,40] anti-Staphylococcus aureus [40,41] and anti-Pseudomonas aeruginosa [41] properties. The dimeric disulfide-based Schiff bases, prepared from 2,2'-dithiodianiline and 2-fluorobenzaldehyde demonstrated especially antibacte-rial action against Gram positive Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli and Actinetobacter baumannii if compared to cefotaxime.…”

“…Aromatic-disulfide based Inhibitors exhibit potent enzymatic activities against SARS-CoV Mpro. [29] Ortho-disubstituted disulfides and their acyl derivatives can be potential candidates as herbicide for weed control in agriculture as they demonstrate broad spectrum of herbicidal effect, [30] the bis-chlorophenyl disulfide was reported to be effective against cancer, [31,32] smallmolecule protein disulfide isomerase (PDI) appeared to inhibit HIV-1 entry into cells. [33] A disulfide derivative allithiamine (thiamine allyl disulfide) is a derivative of vitamin B1 and allicin, which was isolated from garlic (Allium sativum), [34] could alleviate the hyperglycaemia-induced endothelial dysfunction, [35] improve the sensation of neuropathic pain.…”

Synthesis, characterization and antibacterial assays of new N,N 1 -disubstituted 2,2’- dithiodianiline derivatives

“…[25]. A number of diaryl disul de Schiff bases demonstrate antibacterial and herbicidal effect [26−28], the bis-chlorophenyl disul de was reported to be effective against cancer [29,30], small-molecule PDI (protein disul de isomerase) appeared to inhibit HIV-1 entry into cells [31].…”