Synthesis, Dyeing performance and Evaluation of Antimicrobial and Antioxidant Activities of Azo Dye derivatives Incorporated 1,3,4- thiadiazole combined with Molecular Modelling Studies

Abstract

Nowadays, there is significant interest in the synthesis of azo dye derivatives incorporated with heterocyclic scaffolds as a potential scaffold in the pharmaceutical sector, since the incorporation of the heterocyclic moiety into the azo dye has enhanced the bioactive properties of the target derivatives. Herein, six novel azo dye derivatives incorporated with 1,3,4-thiadiazole scaffold were derived from 4-dimethylaminobezaldehyde/4-aminobenzoic acid, thiosemicarbaide and coupling agents (phenol, 1-naphthol, and 2-naphthol) through the conventional diazotization-coupling sequence. The structures of synthesized compounds were characterized and determined with the help of UV-visible, FTIR, 1H NMR and 13C NMR. The interaction, reactivity, physicochemical, pharmacokinetics and toxicity of the compounds were predicted by molecular modelling studies. The azo dyes were tested for their color fastness properties, and compound 136 and 137 displayed excellent fastnesses to washing and rubbing. The synthesized compounds were also evaluated for antimicrobial activity against six bacterial (S.aureus, S.epidermid, E.faecalis, E.coli, K.pnemonia, S.typorumium) and three fungal (C.albicans, T.mentographytes, T.rumbrum) strains by broth dilution method relative to ciprofloxacine and ketoconazole respectively. The antioxidant activity of the synthesized compounds was examined via the DPPH assay method compared to ascorbic acid. Among the tested, compound 136 and 137 showed moderate antimicrobial activities; especially compound 137 showed a good antimicrobial activity (MIC = 0.5 mg/mL) for both bacterial and fungal species compared to ciprofloxacin (0.0005 mg/mL) and ketoconazole (0.005 mg/mL) respectively. Compound 133, displayed potential radical scavenging activity at IC50= 10.7 µg/mL relative to ascorbic acid (IC50= 9.6 µg/mL). In silico molecular interaction displayed that compound 136 exhibited highest binding affinity (-8.0 kcal/mol) to E.coli DNA gyrase B than that of ciprofloxacin (-7.3 kcal/mol). Similarly, the highest binding affinity was shown by compounds 134 and 137 (-6.1 kcal/mol) against S. aureus PK than the standard ciprofloxacin (-4.9 kcal/mole). Compound 137 showed highest binding affinity (-10.6 kcal/mol) with C. albican CYP51 than that of KC (-10.2 kcal/mol). Further, compound 137 showed highest binding affinity (-5.8 kcal/mole) with human peroxidoxins 5 than that of ascorbic acid (-4.2 kcal/mol). Compound 134 revealed lowermost chemical hardness (0.0453 eV) as well as the uppermost softness (22.0751 eV), due to lowest energy gap, which infer highest reactivity of the compound.