Novel pyrazoline linked acyl thiourea pharmacophores as antimicrobial, urease, amylase and α-glucosidase inhibitors: design, synthesis, SAR and molecular docking studies

Abstract

In the present work, a small library of novel pyrazolinyl-acyl thiourea (5a–j) was designed and synthesized through a multistep sequence and the synthesized compounds were screened for their antifungal, antibacterial and antioxidant activities as well as urease, amylase and α-glucosidase inhibitory activities. The synthesized series (5a–o) was characterized using a combination of spectroscopic techniques, including FT-IR, ¹H NMR and ¹³C NMR. All compounds (5a–j) were found to have significant potency against urease, α-glucosidase, α-amylase, and DPPH. The synthesized compounds were also screened for potential antibacterial and anti-fungal inhibition activities. IC₅₀ values for all the prepared compounds for urease, α-glucosidase, amylase, and DPPH inhibition were determined and derivatives 5b and 5g were found to be the most potent urease inhibitors with IC₅₀ values of 54.2 ± 0.32 and 43.6 ± 0.25 μM, respectively. Whilst compound 5b (IC₅₀ = 68.3 ± 0.11 μM) is a potent α-glucosidase inhibitor, compound 5f (90.3 ± 1.08 μM) is a potent amylase inhibitor and compound 5b (103.4 ± 1.15 μM) is a potent antioxidant. The different substitutions on the phenyl ring were the basis for structure–activity relationship (SAR) study. The molecular docking study was performed for the confirmation of binding interactions.