Дизайн, синтез, in silico та in vitro дослідження похідних 4-ціано-2-феніл-1,3-оксазол-5-сульфонаміду

• Дата: 2024
• Автори: Pilyo, Stepan G., Kachaeva, Maryna V., Severin, Oleksandr O., Kozachenko, Oleksandr P., Zhirnov, Victor V., Brovarets, Volodymyr S.
• Формат: Стаття
• Опубліковано: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2024
• Теми: 4-cyano-2-phenyl-1,3-oxazole-5-sulfonamides; anticancer activity; SAR analysis; COMPARE correlation; ADMET analysis; 4-ціано-2-феніл-1,3-оксазол-5-сульфонаміди; протиракова активність; SAR аналіз; COMPARE кореляція; ADMET аналіз
• Онлайн доступ: https://bioorganica.com.ua/index.php/journal/article/view/82
• Назва журналу: Ukrainica Bioorganica Acta

A thirteen 4-cyano-2-phenyl-1,3-oxazole-5-sulfonamide analogs have been synthesized and characterized by spectroscopy methods, elemental analysis. Their growth inhibiting activity was determined in vitro in the one dose assay against the total NCI-60 human cancer cell line panel. The five-dose analysis was performed on the six compounds with greater cytotoxicity. Two compounds 8 and 9 exhibited the greatest potency against total NCI-60 cancer cell lines in the five dose assay. Furthermore, compound 9 with 3 methylpiperidine fragment turned out to be two times more active than compound 8 with 4-methylpiperidine (GI50 = 1.4±0.1 against 2.5±0.4, GI = 3.9±0.6 against 7.1±1.3 and LC50 = 7.1±1.0 against 16.4±2.3 µM). The lack of commonly used drugs that show a high correlation with the majority of analyzed compounds, based on two out of three calculated parameters of anticancer potency, suggests that they may interact with a unique target. The ADMET analysis results predict that this compound meets the drug similarity criteria and does not belong to interfering molecules that react non-specifically with numerous targets. The prediction of lead likeness for all compounds is also included, meaning that any of them can be optimized to enhance selectivity and other pharmacological properties that characterize their chemotherapeutic potential