Design, Molecular Docking and Synthesis of Pyrazino[1,2-A] Indole Derivatives Via Tandem Ugi-4Cr/Intramolecular Cyclization As Potential Urease Inhibitor Agents Publisher



Shourkaei FA¹ ; Lish AB² ; Talebi M³ ; Abdoli S³ ; Zare N³ ; Amanlou M^{3, 4} ; Ranjbar PR¹ ; Mahdavi M⁵ Show Affiliations
Source: Journal of Molecular Structure Published:2024

Abstract

In the present paper, a novel series of pyrazino[1,2-a]indole derivatives 6(a-k) were synthesized by Ugi four-component reaction (U-4CR), followed by an intramolecular cyclization of the Ugi products in the presence of DBU as a catalyst, Subsequently, we assessed their inhibitory activity against Jack bean's urease enzyme in vitro, and some of these derivatives exhibited potent urease inhibition. Notably, compounds 6e (IC50 = 3.55 ± 1.11 µM), 6g (IC50 = 3.18 ± 0.42 µM), and 6j (IC50 = 3.80 ± 0.65 µM) demonstrated urease inhibitory effects comparable to the reference compound, thiourea. Additionally, our docking study corroborated these experimental results, confirming that the pyrazino[1,2-a]indole derivatives (6a-k) effectively interacted with the urease enzyme's active site, exhibiting proper binding energies and modes. © 2023