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

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.

Modeling of Anticancer Sulfonamide Derivatives Lipophilicity by Chemometric and Quantitative Structure-Retention Relationships Approaches

“…The anticancer potential against the HCT-116 cell line has also been demonstrated by N-acylated benzenesulfonamides, which contained at the benzene ring the 1-naphthylmethylthio substituent and the sulfonamidic nitrogen atom bonded to acetic acid or cinnamic acid residues [30]. Similarly, fused pyrimidine hybrids of myrrhanone C and Argentatins A-C showed noticeable anticancer activity against several human cancer cell lines [31,32]. The main goal of this study was to assess the sulfonamide derivatives with proven anticancer activities against human colon cancer (HCT-116) using a chromatographic approach.…”

Antiskin Aging Effects of Indole AlkaloidN-Glycoside from Ginkgo Fruit (Ginkgo bilobafruit) on TNF-α-Exposed Human Dermal Fibroblasts

“…Based on this hypothesis, we have been researching natural products that can suppress TNFα stimulated human dermal fibroblast (HDF) damage, 7−10 since natural products with diverse chemical skeletons have been an important source for drug discovery. 11,12 Ginkgo biloba L. (Ginkgoaceae), one of the most famous medicinal plants, is referred to as a "living fossil" as it is the single surviving species of the Ginkgo family. 13 G. biloba, the oldest living plant species, is native to China and it is also distributed in Korea and Japan.…”

“…As skin aging progresses, dermal fibroblasts produce tumor necrosis factor (TNF)-α, which is associated with skin aging and an increase in collagenase matrix metalloprotease (MMP) and pro-inflammatory factors. , Thus, dermal fibroblasts exposed to TNF-α may exhibit skin aging. Based on this hypothesis, we have been researching natural products that can suppress TNF-α stimulated human dermal fibroblast (HDF) damage, − since natural products with diverse chemical skeletons have been an important source for drug discovery. , …”

Efficient access to domain-integrated estradiol-flavone hybrids via the corresponding chalcones and their in vitro anticancer potential

“…The concept of molecular hybridization, which involves the creation of a new molecule by combining two or more structural subunits of different bioactive compounds, offers an excellent opportunity for the chemical modifications of natural compounds [1][2][3][4][5][6][7]. Hybrid drugs provide a state-of-the-art therapeutic option for a variety of diseases, such as cancer, and unlike many conventional treatments, may display higher and more selective activity, including the elimination of drug resistance and the reduction of unwanted side effects.…”