TY - JOUR
T1 - Semi-synthesis and cytotoxicity evaluation of pyrimidine, thiazole, and indole analogues of argentatins A–C from guayule (Parthenium argentatum) resin
AU - Madasu, Chandrashekhar
AU - Xu, Ya Ming
AU - Wijeratne, E. M.Kithsiri
AU - Liu, Manping X.
AU - Molnár, István
AU - Gunatilaka, A. A.Leslie
N1 - Funding Information:
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.
PY - 2022/7
Y1 - 2022/7
N2 - 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.]
AB - 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.]
KW - Argentatins A–C
KW - Cytotoxic activity
KW - Guayule resin
KW - Indole analogues
KW - Pyrimidine analogues
KW - Thiazole analogues
UR - http://www.scopus.com/inward/record.url?scp=85123086130&partnerID=8YFLogxK
U2 - 10.1007/s00044-021-02835-1
DO - 10.1007/s00044-021-02835-1
M3 - Article
AN - SCOPUS:85123086130
SN - 1054-2523
VL - 31
SP - 1088
EP - 1098
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 7
ER -