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Semi-synthesis and cytotoxicity evaluation of pyrimidine, thiazole, and indole analogues of argentatins A–C from guayule (Parthenium argentatum) resin

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Abstract

Argentatins A–C (1–3), the major cycloartane-type triterpenoids of guayule resin, a byproduct of commercial rubber production, were converted into their pyrimidine (7–12), thiazole (13–15), and indole (16–18) analogues by a molecular hybridization approach. The cytotoxic activities of these fused heterocyclic analogues 7–18 were compared with those of argentatins A–C (1–3) against a panel of three sentinel human cancer cell lines [NCI-H460 (non-small cell lung), MCF-7 (breast adenocarcinoma), and SF-268 (central nervous system glioma)], and normal human fibroblast (WI-38) cells. The cytotoxicity data suggest that the pyrimidine analogues 7 and 8 (derived from 1), 9 and 10 (derived from 2), and 12 (derived from 3) had significantly enhanced activity compared to the parent compounds or their thiazole (13–15) and indole (16–18) analogues. These findings indicate that triterpenoid constituents of guayule resin may be exploited to obtain value-added products with potential applications in anticancer drug discovery.

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Acknowledgements

This project was supported by the USDA-NIFA (Grant # 2017-68005-26867; Kimberly Ogden, PI) and Hatch projects ARZT-1005072 (AALG) and ARZT-1361640-H12-224 (IM), and the University of Arizona College of Agriculture. Any opinions, findings, conclusions, or recommendations expressed in this publication/work are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture. We thank Dr. Lijiang Xuan, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, P. R. China for HRMS data.

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Authors and Affiliations

  1. Southwest Center for Natural Products Research, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, AZ, 85706, USA

    Chandrashekhar Madasu, Ya-Ming Xu, E. M. Kithsiri Wijeratne, Manping X. Liu, István Molnár & A. A. Leslie Gunatilaka

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  1. Chandrashekhar Madasu
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Correspondence to A. A. Leslie Gunatilaka.

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IM has disclosed financial interests in TEVA Pharmaceuticals Hungary and the University of Debrecen, Hungary, which are unrelated to the subject of the research presented here. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Madasu, C., Xu, YM., Wijeratne, E.M.K. et al. Semi-synthesis and cytotoxicity evaluation of pyrimidine, thiazole, and indole analogues of argentatins A–C from guayule (Parthenium argentatum) resin. Med Chem Res 31, 1088–1098 (2022). https://doi.org/10.1007/s00044-021-02835-1

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