Inhibition potential of phenyl linked benzimidazole-triazolothiadiazole modular hybrids against β-glucuronidase and their interactions thereof

β-Glucuronidase is responsible for the catalytic deconjugation of β-D-glucuronides. β-Glucuronidase has evolved to be a viable molecular target for numerous therapeutic treatments. It plays a pivotal role in the metabolism of drugs and endogenous substances. Herein, we report the inhibitory potentials of newly developed and modular benzimidazole-triazolothiadiazole hybrids spaced through a phenyl linker (1–26) and their interactions with the β-glucuronidase. All analogues showed IC₅₀ values in the range of 1.30 ± 0.10 to 44.10 ± 0.80 μM, and hence were found to have outstanding inhibitory potential as compare to the standard D-saccharic acid 1,4-lactone (IC₅₀ = 48.4 ± 1.25 μM). These modular hybrids were successfully synthesized, rigorously characterized through various spectroscopic techniques. Molecular docking studies further revealed the potential interactions between the inhibitor and active amino acid site in β-glucuronidase. These findings helped in identifying the potential for new drug candidates. A Plausible structure activity relationship (SAR) were established which suggested that variation in the inhibitory potential was mainly based upon the substituents attached to the phenyl ring.