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

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 alpha-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, alpha-glucosidase, alpha-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, alpha-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 mu M, respectively. Whilst compound 5b (IC50 = 68.3 +/- 0.11 mu M) is a potent alpha-glucosidase inhibitor, compound 5f (90.3 +/- 1.08 mu M) is a potent amylase inhibitor and compound 5b (103.4 +/- 1.15 mu M) 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. IC50 values of the new synthesized pyrazoline-acyl thioureas revealed 5b and 5g as potent urease inhibitors. Whilst compound 5b is a potent alpha-glucosidase inhibitor, compound 5f is a potent amylase inhibitor, compound 5b is a potent antioxidant.