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. [Figure not available: see fulltext.]
Original language | English |
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Pages (from-to) | 1088-1098 |
Number of pages | 11 |
Journal | Medicinal Chemistry Research |
Volume | 31 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 2022 |
MoE publication type | A1 Journal article-refereed |
Funding
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. We thank Dr. Lijiang Xuan, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, P. R. China for HRMS data.
Keywords
- Argentatins A–C
- Cytotoxic activity
- Guayule resin
- Indole analogues
- Pyrimidine analogues
- Thiazole analogues