Current computer-aided drug design · 2026
Synthesis and Computational Analysis of Para-fluorinated Phenoxymethyl Benzenesulfonamides as Potential CETP Inhibitors.
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.
Abu Khalaf Reema, Abu Al-Haj Lana, Hajjo Rima, Al-Sha'er Mahmoud A
Аннотация
BACKGROUND: Dyslipidemia is a major risk factor for the development and progression of coronary artery disease. It results from an abnormal increase in low-density lipoprotein cholesterol, cholesteryl esters, or triglyceride levels in the blood. Cholesteryl ester transfer protein (CETP) is a protein that promotes the bidirectional allocation of triglycerides and cholesteryl esters between lipoproteins in the blood. CETP inhibition reduced dyslipidemia.
OBJECTIVE: This work describes the synthesis, computational characterization, and CETP inhibitory activity of ten para-fluorinated phenoxymethyl benzenesulfonamides (6a-6j).
METHODS: Compounds 6a-6j were characterized using various spectroscopic techniques and subsequently evaluated using computational analysis and biological assays.
RESULTS: The compounds showed in vitro CETP % inhibition ranging from 4.2% to 100% at 10 μM. Among them, compound 6g (para-chloro substituted) demonstrated complete CETP inhibition (100 ± 1.2%), the highest pharmacophore fit value (7.72), and strong docking affinity (LibDock = 144.35; -CDocker = 0.24). Compounds 6e and 6f (ortho- and meta-chloro analogs) also exhibited high inhibitory activity (67% and 72%, respectively) with good docking scores (LibDock: 135.16 and 148.65; fit values: 2.02 and 6.84, respectively). Conversely, the unsubstituted derivative 6a exhibited minimal inhibition (4.2%) and fit/docking scores (LibDock = 140.21; fit = 2.09).
DISCUSSION: Cheminformatics, PCA, and descriptor-loading analyses provided insight into the chemical space defined by the descriptors and the structural diversity of the synthesized compounds. Overall, compounds with higher CETP inhibitory activity generally exhibited more favorable docking interactions and higher pharmacophore fit values. Electron-withdrawing chloro substituents may promote favorable interactions within the hydrophobic CETP binding pocket.
CONCLUSION: These findings suggest that electronic effects, substituent orientation, and hydrophobic properties contribute to CETP inhibitory activity, providing a foundation for future optimization and biological evaluation of sulfonamide-based CETP inhibitors.
OBJECTIVE: This work describes the synthesis, computational characterization, and CETP inhibitory activity of ten para-fluorinated phenoxymethyl benzenesulfonamides (6a-6j).
METHODS: Compounds 6a-6j were characterized using various spectroscopic techniques and subsequently evaluated using computational analysis and biological assays.
RESULTS: The compounds showed in vitro CETP % inhibition ranging from 4.2% to 100% at 10 μM. Among them, compound 6g (para-chloro substituted) demonstrated complete CETP inhibition (100 ± 1.2%), the highest pharmacophore fit value (7.72), and strong docking affinity (LibDock = 144.35; -CDocker = 0.24). Compounds 6e and 6f (ortho- and meta-chloro analogs) also exhibited high inhibitory activity (67% and 72%, respectively) with good docking scores (LibDock: 135.16 and 148.65; fit values: 2.02 and 6.84, respectively). Conversely, the unsubstituted derivative 6a exhibited minimal inhibition (4.2%) and fit/docking scores (LibDock = 140.21; fit = 2.09).
DISCUSSION: Cheminformatics, PCA, and descriptor-loading analyses provided insight into the chemical space defined by the descriptors and the structural diversity of the synthesized compounds. Overall, compounds with higher CETP inhibitory activity generally exhibited more favorable docking interactions and higher pharmacophore fit values. Electron-withdrawing chloro substituents may promote favorable interactions within the hydrophobic CETP binding pocket.
CONCLUSION: These findings suggest that electronic effects, substituent orientation, and hydrophobic properties contribute to CETP inhibitory activity, providing a foundation for future optimization and biological evaluation of sulfonamide-based CETP inhibitors.