Future medicinal chemistry · 2025
Discovery of isatin-thiazole conjugates as potent urease inhibitors; synthesis, biochemical screening and computational studies.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Haider Mian Bilal, Zaib Sumera, Saeed Aamer, Ahmed Atteeque, Javed Hira, Areeba, Shabir Ghulam, Irfan Madiha, Othman Gehan Ahmed
Аннотация
AIM: Urease is essential to Helicobacter pylori metabolism and plays role in stomach cancer, gastritis, peptic ulcer, hepatic coma, urinary tract infection, liver encephalopathy, and pyelonephritis. Therefore, inhibition of urease is an appealing approach to treat bacterial infections.
MATERIALS AND METHODS: The present work describes the synthesis of a series of ten new bioactive isatin-thiazole conjugates (5a-j). The target adducts were characterized using fourier transform infrared (FT-IR), 1H- and 13C- nuclear magnetic resonance imaging (NMR) spectroscopy. The compounds were obtained using a multistep strategy that included nitration, alkylation, condensation and cyclization sequence. Subsequently, these compounds were screened for their urease inhibition potential.
RESULTS AND CONCLUSION: All the compounds showed better inhibitory potential than the positive control, thiourea with IC50 ranging from 0.44 to 8.70 µM. However, compound 5j exhibited an excellent non-competitive urease inhibitory effect with an IC50 value of 0.44 ± 0.23 µM. Apart from in vitro investigation, the molecular docking revealed a strong affinity of 5j within the active site of urease exhibiting a binding energy of -7.9 kcal/mol. Succinctly, the lead inhibitor 5j exhibited noteworthy IC50 and effective binding free energy which emphasizes its strong binding potential. .
MATERIALS AND METHODS: The present work describes the synthesis of a series of ten new bioactive isatin-thiazole conjugates (5a-j). The target adducts were characterized using fourier transform infrared (FT-IR), 1H- and 13C- nuclear magnetic resonance imaging (NMR) spectroscopy. The compounds were obtained using a multistep strategy that included nitration, alkylation, condensation and cyclization sequence. Subsequently, these compounds were screened for their urease inhibition potential.
RESULTS AND CONCLUSION: All the compounds showed better inhibitory potential than the positive control, thiourea with IC50 ranging from 0.44 to 8.70 µM. However, compound 5j exhibited an excellent non-competitive urease inhibitory effect with an IC50 value of 0.44 ± 0.23 µM. Apart from in vitro investigation, the molecular docking revealed a strong affinity of 5j within the active site of urease exhibiting a binding energy of -7.9 kcal/mol. Succinctly, the lead inhibitor 5j exhibited noteworthy IC50 and effective binding free energy which emphasizes its strong binding potential. .