Future medicinal chemistry · 2026
Newly synthesized 2-cyclopentylidenehydrazinylthiazoles as potential therapeutic agents against peptic ulcer.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sehrish, Salar Uzma, Naz Farzana, Ishaq Aqsa, Naz Fouzia, Iqbal Jamshed, Khan Khalid Mohammed
Аннотация
BACKGROUND: Urease increases the stomach's pH by hydrolyzing urea and fostering the growth of Helicobacter pylori, linked to a variety of gastrointestinal issues, including peptic ulcers. Despite the availability of conventional therapies, the development of safe and effective, nontoxic urease inhibitors with better pharmacological profiles remains an unmet need.
METHODS: Novel 2-cyclopentylidenehydr azinyl thiazole derivatives were first time synthesized by first reacting cyclopentanone with thiosemicarbazide to afford thiosemicarbazone which then treated with different phenacyl bromides to afford products.
RESULTS: All compounds exhibited outstanding urease inhibitory activity (IC50 = 0.14 to 6.39 µM) than the standard inhibitors thiourea and acetohydroxamic acid (AHA), with IC50 values of 19.43 and 41.3 µM, respectively. In fact, CH3 bearing compound 10 (IC50 = 0.04 ± 0.008 µM) exhibited the highest inhibitory potential against urease. Structure-activity relationship (SAR) indicated that the inhibitory potential is strongly influenced by the electronic and steric factors. Furthermore, molecular docking experiments also revealed various interactions between the ligands (compounds) and the enzyme's active site. Detailed pharmacokinetics, drug-likeness, and absorption, distribution, metabolism, and excretion (ADME) properties were also assessed.
CONCLUSION: This study demonstrates that these newly synthesized thiazole derivatives may serve as potential lead candidates for the discovery of antiulcer agents.
METHODS: Novel 2-cyclopentylidenehydr azinyl thiazole derivatives were first time synthesized by first reacting cyclopentanone with thiosemicarbazide to afford thiosemicarbazone which then treated with different phenacyl bromides to afford products.
RESULTS: All compounds exhibited outstanding urease inhibitory activity (IC50 = 0.14 to 6.39 µM) than the standard inhibitors thiourea and acetohydroxamic acid (AHA), with IC50 values of 19.43 and 41.3 µM, respectively. In fact, CH3 bearing compound 10 (IC50 = 0.04 ± 0.008 µM) exhibited the highest inhibitory potential against urease. Structure-activity relationship (SAR) indicated that the inhibitory potential is strongly influenced by the electronic and steric factors. Furthermore, molecular docking experiments also revealed various interactions between the ligands (compounds) and the enzyme's active site. Detailed pharmacokinetics, drug-likeness, and absorption, distribution, metabolism, and excretion (ADME) properties were also assessed.
CONCLUSION: This study demonstrates that these newly synthesized thiazole derivatives may serve as potential lead candidates for the discovery of antiulcer agents.