New thioxothiazolidinyl-acetamides derivatives as potent urease inhibitors: design, synthesis, in vitro inhibition, and molecular dynamic simulation

Abstract

To identify potent urease inhibitors, in the current study, a series of thioxothiazolidinyl-acetamides were designed and synthesized. The prepared compounds were characterized by spectroscopic techniques, including FTIR, 1HNMR, 13CNMR, and elemental analysis. In the enzymatic assessments, it was demonstrated that all derivatives had significant urease inhibition with IC50 values in the range of 1.473–9.274 µM in comparison with the positive control hydroxyurea (IC50 = 100.21 ± 2.5 µM) and thiourea (IC50 = 23.62 ± 0.84 µM). Compound 6i (N-benzyl-3-butyl-4-oxo-2-thioxothiazolidine-5-carboxamide) was the most active agent with an IC50 value of 1.473 µM. Additionally, kinetic investigation and in silico assessments of 6i was carried out to understand the type of inhibition and behavior of the most potent derivative within the binding site of the enzyme. Noteworthy, the anti-urease assay against P. vulgaris revealed 6e and 6i as the most active agents with IC50 values of 15.27 ± 2.40 and 17.78 ± 3.75 µg/mL, respectively. Antimicrobial evaluations of all compounds reveal that compounds 6n and 6o were the most potent antimicrobial agents against the standard and resistant S. aureus. 6n and 6o also showed 37 and 27% inhibition in the development of biofilm by S. aureus at 512 µg/ml. Furthermore, the MTT test showed no toxicity up to 100 µM. Taken together, the study suggests that the synthesized thioxothiazolidinyl-acetamides bases derivatives may serve as potential hits as urease inhibitors.

Potentiometric determination of urea in fermented alcoholic beverages commonly consumed in India using biosensor by immobilization of urease on nylon membrane using Ammonium Ion Selective Electrode (AISE)

“…Numerous creatures, including bacteria, fungi, plants, and mammals, contain it. One of the most researched enzymes, urease has numerous uses in the food, pharmaceutical, and agricultural industries [5].…”

Exploring the Synthetic Chemistry of Phenyl-3-(5-aryl-2-furyl)- 2-propen-1-ones as Urease Inhibitors: Mechanistic Approach through Urease Inhibition, Molecular Docking and Structure–Activity Relationship

“…Generally, natural and synthetic heterocycles are privileged derivatives [ 7 , 8 ], such as furans [ 9 ], quinoxalines [ 10 ], coumarins [ 11 ], benzimidazoles [ 12 ], heterocyclic sulfonamides [ 13 ], theophyllines [ 14 ], imidazoles [ 15 ], pyrazoles [ 16 ], thiadiazoles [ 17 ], etc., which demonstrate wide-spectrum biological activities in the fields of pharmacology, medicinal chemistry, pharmaceutical chemistry, and pharmaceutics. In the same way, various heterocyclic synthetic compounds have been designed to compete with the growing challenges related to ureolytic microorganisms, including thioureas [ 18 ], triazoles [ 19 ], thiadiazoles [ 20 ], benzimidazoles [ 21 ], hydroxamic acid [ 22 ], phosphoramidate, and thiazolacetamide [ 23 ].…”

Синтез Уреїдних Похідних 2-Аміно-3-Карбетокси(ціано)тіофенів І Вивчення Їх Циклізації

“…Нині у світі однією з найпоширеніших причин смерті є онкологічні захворювання, докладаються великі зусилля для пошуку нових біологічно активних речовин для відкриття на їхній основі нових протипухлинних засобів. Наявні на сьогоднішній день протипухлинні препарати мають токсичність, ефект лікарської взаємодії та резистентність, через що активно ведеться пошук нових протипухлинних препаратів (El-Metwally, 2021; Dastyafteh, 2023).…”