Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Molecules. 2020 Mar 17;25(6):1367. doi: 10.3390/molecules25061367.
Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO and WS assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO approach as being more convenient in the field of drug metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization.
建立药物在肝生物转化途径中的代谢途径是临床前发现过程中最重要的方面之一，因为有毒或反应性代谢物的存在可能导致药物从市场上撤出。在这项研究中，我们提出了一种新型光催化方法，使用 WO 和 WS 辅助光化学反应，对一种抗精神病药物莫林酮的六种尚未描述的代谢物进行结构阐明。UHPLC-ESI-Q-TOF 联合系统用于记录所有获得的代谢产物谱，并记录观察到的转化产物的高分辨碎裂光谱。作为体外代谢模拟方法的参考，使用人肝微粒体孵育。获得的图谱的化学计量比较指出，在药物代谢研究领域，WO 方法更方便。此外，光催化用于主要药物代谢物合成的方向，以进一步进行分离和表征。
