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Synthesis of oleanolic acid/ursolic acid/glycyrrhetinic acid-hydrogen sulfide donor hybrids and their antitumor activity

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Abstract

A total of 25 targeted hydrogen sulfide donor–pentacyclic triterpene hybrids were designed, synthesized and evaluated on the basis of inspiring reports about hydrogen sulfide donor molecules and oleanolic acid derivatives on anti-tumor activity. The results revealed that only some hybrids (10a, 10b, 12a, 12b, 13a, and 15b) showed moderate anti-proliferation activity against K562 cell line. It indicated that oleanane-type, (R)-lipoic acid and TBZ groups were much more favorable to the anti-proliferation activity. Furthermore, C-3 OH was more beneficial than C-28/29 COOH in the oleanane-type to the antitumor activity of the batch of (R)-lipoic acid derivatives. And among them, only compound 13a exhibited moderate anti-proliferation activity against both K562 and K562/ADR cell lines, while it exhibited no anti-proliferation activity against BEL-7402 and L-O2 cell lines. Therefore, it suggested that it was not suitable for hybridization of hydrogen sulfide donors attached to oleanolic acid, ursolic acid and glycyrrhetinic acid in the field of anti-tumor.

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Acknowledgements

This study was financially supported by grants from the National Natural Science Foundation of PRC (21562006), Guangxi Natural Science Foundation of China (2015GXNSFAA139186), Guangxi′s Medicine Talented Persons Small Highland Foundation (1506), Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University), and Ministry of Education of China (CMEMR2013-A01, CMEMR2013-C02), and IRT_16R15.

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  1. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy of Guangxi Normal University, 541004, Guilin, P. R. China

    Li-xin Sheng, Jia-yan Huang, Chun-mei Liu, Ju-zheng Zhang & Ke-guang Cheng

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  1. Li-xin Sheng
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  2. Jia-yan Huang
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  3. Chun-mei Liu
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  4. Ju-zheng Zhang
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  5. Ke-guang Cheng
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Correspondence to Ke-guang Cheng.

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Sheng, Lx., Huang, Jy., Liu, Cm. et al. Synthesis of oleanolic acid/ursolic acid/glycyrrhetinic acid-hydrogen sulfide donor hybrids and their antitumor activity. Med Chem Res 28, 1212–1222 (2019). https://doi.org/10.1007/s00044-019-02366-w

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  • DOI: https://doi.org/10.1007/s00044-019-02366-w

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