Synthesis, antifungal studies, molecular docking, ADME and DNA interaction studies of 4-hydroxyphenyl benzothiazole linked 1,2,3-triazoles

Abstract

In search of new bioactive 1,2,3-triazole hybrids, some 4-hydroxyphenyl benzothiazole (4-HBT) linked 1,2,3-triazole with varying lengths of alkyl spacers were synthesized from bromo alkoxy derivatives of 4-HBT. All the synthesized hybrids were satisfactorily characterized, and were evaluated for in-vitro antifungal activity against C. tropicalis and A. terreus fungal strains wherein compound 4 h showed better activity for both fungal strains compared to the reference drug Fluconazole. Molecular docking with the active site of 14α-sterol demethylase enzyme (PDBID: 1EA1) showed that all compounds exhibited strong H-bonding interactions with Thr260, Ala256, Arg96, Phe78, Leu321, Tyr76 while compound 4 h with the lone pair of -Cl have shown better interaction with the active site and were involved in H-bond interaction with THR 260. DNA binding study exhibited very good DNA-interaction (2.03 × 105 Lmol-1) of compound 4b with the hs-DNA. The results of DFT study and ADME investigations were accessed for the pharmacodynamics and pharmacokinetic properties of the synthesized molecules.