Abstract
•Synthesis of new triazinoindole bearing bis-Schiff base derivatives and fully characterized by various spectroscopic techniques.•In vitro screening against β-glucuronidase inhibitors.•Identification of a new class of β-glucuronidase inhibitors.•Structure activity relationship was established to understand the contribution of different substituents.•In silico studies of most active compounds were performed to understand the binding interactions with enzyme.
Triazinoindole bearing bis-Schiff base analogs (1–20) were synthesized by triazinoindole-thione ring formation, triazinoindole-thiol-phenylethanone, followed by triazinoindole bis-Schiff base formation. Synthesized analogs showed β-glucuronidase potential with IC50 value ranging between 2.60 ± 0.10 to 55.40 ± 1.60 µM as compared to standard d-saccharic acid 1,4-lactone (IC50 = 48.10 ± 1.2 µM). Analog 20 was the most potent one with IC50 value 2.60 ± 0.10 µM. Analogs 17, 4 showed IC50 values 5.20 ± 0.20 and 5.70 ± 0.20 µM respectively and withstand 2nd and 3rd ranked scaffolds among the synthesized analogs. All other sixteen analogs showed many-fold better potency with IC50 values ranging from 7.9 ± 0.2 to 48.1 ± 1.2 µM. The structure-activity relationship was established and confirmed of binding interactions through molecular docking studies.