National Institute of Pharmaceutical Education and Research-Ahmedabad, An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Airforce Station, Palaj, Gandhinagar, Gujarat, India.
Department of Pharmaceutical Analysis, India.
Biomed Chromatogr. 2021 Jun;35(6):e5082. doi: 10.1002/bmc.5082. Epub 2021 Feb 14.
IMID-2, a newly identified piperazine-based anticancer molecule, has been shown to be cytotoxic against various cancer cell lines. The primary aim of this research was to identify and characterize possible metabolites of the molecule formed during biotransformation. A metabolite identification study was first executed using an in silico tool to predict the possible metabolism sites of IMID-2. Thereafter, metabolites generated in vitro (rat liver microsomes, rat S9 fractions and human liver microsomes) and in vivo (rat plasma, urine and feces) were identified and characterized employing UPLC-QTOF-MS/MS. A total of eight metabolites, among which were six in phase I and two in phase II reactions, were recognized. The plausible structure of the metabolites and probable metabolic pathway have been established based on the mass fragmentation pattern, mass ppm error, ring double bond calculation and nitrogen rule. The majority of phase I metabolites were generated by N-oxidation, hydroxylation, oxidative deamination followed by reduction, oxidative dechlorination, N-dearylation, and N-dealkylation. Glucuronidation played a significant role in the formation of phase II metabolites of the molecule.
IMID-2，一种新鉴定的哌嗪类抗癌分子，已被证明对各种癌细胞系具有细胞毒性。本研究的主要目的是鉴定和表征在生物转化过程中形成的分子的可能代谢物。首先使用计算工具进行代谢物鉴定研究，以预测 IMID-2 的可能代谢部位。此后，使用 UPLC-QTOF-MS/MS 鉴定和表征了在体外（大鼠肝微粒体、大鼠 S9 级分和人肝微粒体）和体内（大鼠血浆、尿液和粪便）生成的代谢物。共鉴定出 8 种代谢物，其中 6 种为 I 相反应，2 种为 II 相反应。根据质量碎片模式、质量 ppm 误差、环双键计算和氮规则，确定了代谢物的可能结构和可能的代谢途径。大多数 I 相代谢物是通过 N-氧化、羟化、氧化脱氨随后还原、氧化脱氯、N-去酰化和 N-脱烷基化生成的。该分子的 II 相代谢物的形成主要涉及葡萄糖醛酸化。
