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Metabolism and disposition of a novel antineoplastic JS-38 (Benzamide, N-[4-(2,4-dimethoxyphenyl)-4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl]-3,5-bis (trifluoromethyl)-(9Cl)) in rats

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Abstract

The metabolism and catabolism of a novel antineoplastic (ID code JS-38),Benzamide, N-[4-(2,4-dimethoxyphenyl)-4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl]-3,5-bis (trifluoromethyl)-(9Cl), were investigated in Wistar rats (3 female, 3 male). LC/UV, LC/MS, LC/MS/MS, NMR and acid hydrolysis methods showed that the metabolic process of JS-38 consists of a series of acetylation and glucoronation that form a metabolic product with a unique pharmacologic property of accelerating bone-marrow cell formation, and also showed a novel metabolic pathway of being acetylated and glucuronated in series.

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Acknowledgments

We acknowledge professor Danyu Hua, Yue Li and Tong Wu of Shanghai Institute of Pharmaceutical Industry for NMR detection and good advice; Xiangwei Wang of Medicilon Ltd. for MS detection; Gangyi Liu of Shanghai Xuhui Central Hospital for LC/MS/MS detection.

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Authors and Affiliations

  1. Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, China

    Hong Zhang, Tingting Fan, Yu Fang & Ying Li

  2. Shanghai Institute of Pharmaceutical Industry, Shanghai, China

    Quanhai Liu & Guoping Wang

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  1. Hong Zhang
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  2. Quanhai Liu
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  3. Tingting Fan
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  4. Yu Fang
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  5. Ying Li
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Correspondence to Hong Zhang.

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Zhang, H., Liu, Q., Fan, T. et al. Metabolism and disposition of a novel antineoplastic JS-38 (Benzamide, N-[4-(2,4-dimethoxyphenyl)-4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl]-3,5-bis (trifluoromethyl)-(9Cl)) in rats. Eur J Drug Metab Pharmacokinet 37, 45–56 (2012). https://doi.org/10.1007/s13318-011-0055-8

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  • DOI: https://doi.org/10.1007/s13318-011-0055-8

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