Synthesis and Identification of New N,N-Disubstituted Thiourea, and Thiazolidinone Scaffolds Based on Quinolone Moiety as Urease Inhibitor

Abstract

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N,N-disubstituted thioureas. Finally, on subjecting the N,N-disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N,N-disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure−activity relationship revealed that N-methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein−ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N,N-disubstituted thiourea.

Convenient synthesis and X-ray determination of 2-amino-6H-1,3,4-thiadiazin-3-ium bromides endowed with antiproliferative activity

“…The human mammary gland epithelial (MCF-10A) normal cell line was used to investigate the viability effect of new targets 9a–g on viability. 46,47 Refer to Appendix A for more details.…”

Urease Inhibition and Structure‐Activity Relationship Study of Thiazolidinone‐, Triazole‐, and Benzothiazole‐Based Heterocyclic Derivatives: A Focus Review

“…Elshaier et al [83] . synthesized quinolone based derivatives of thiazolidinone 8 and tested them for their in vitro antiurease activity ( Canavalia ensiformis ).…”

“…Elshaier et al [83] synthesized quinolone based derivatives of thiazolidinone 8 and tested them for their in vitro antiurease activity (Canavalia ensiformis). Results found that the tested compounds exhibited moderate urease inhibitory potential (IC 50 = 18.80-45.43 μM).…”

Design and Synthesis of 2-(4-Bromophenyl)Quinoline-4-Carbohydrazide Derivatives via Molecular Hybridization as Novel Microbial DNA-Gyrase Inhibitors

“…They have reported to act as inhibitors of DNA gyrase, topoisomerase, and as urease inhibitors. 2,28,31 1.1. Rational of the Design.…”

“…Compounds incorporating quinoline-based bioactive heterocycles such as pyrrole, pyrazoline, or benzopyrrole rings have drawn considerable attention with pronounced antimicrobial effect. − These compounds were utilized as broad spectrum antibiotic drugs that work on both Gram-positive and Gram-negative pathogens as well as many fungal strains. − The antimicrobial effect of these classes of compounds is mediated through different mechanisms. They have reported to act as inhibitors of DNA gyrase, topoisomerase, and as urease inhibitors. ,, …”