In vitro enzymatic, in silico ADME and molecular docking based analysis for the identification of novel bis-indole containing triazine-thiazole hybrids derivatives as promising urease inhibitors

Abstract

The current study details a sequence of sequential reactions for synthesizing bis-indole-based triazine bearing thiazole derivatives. Several steps were involved in the synthesis of bis-indole-based triazine bearing thiazole derivative. The synthetic reactions were monitored via thin-layer chromatography (TLC). Synthesized compounds were characterized using various spectroscopic techniques, including ¹H NMR, ¹³C NMR, and HR-EIMS. The inhibitory activity against urease enzyme of these synthesized compounds was compared with that of thiourea, a standard drug (IC₅₀ = 9.30 ± 0.20 µM). A range of inhibitory potencies were observed for the synthesized compounds, ranging from moderate to excellent, as follows (IC₅₀ = 5.10 ± 0.40 µM to 29.80 ± 0.20 µM). Analyzing the structure-activity relationship (SAR) provided insight into the results, showing that different substituents had different effects on aromatic rings. Several compounds displayed outstanding inhibitory properties (among those tested were 1, 2, 4, 5, and 6 with IC₅₀ = 6.30 ± 0.80, 5.10 ± 0.40, 5.90 ± 0.50, 8.20 ± 0.10, 8.90 ± 0.60 µM, respectively). Anti-urease evaluation of all the synthesized derivatives was conducted in which the selected compounds have shown remarkable potency compared with the standard drug thiourea (IC₅₀ = 9.30 ± 0.20 µM). Molecular docking analysis was carried out for investigating the better binding sites and distance of the derivatives. Moreover, the drug-like properties were explored by the ADME attributes of the synthesized analogs.

Keywords: SAR and molecular docking; indole; thiazole; triazine; urease.