Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng-derived natural product, panaxytriol

Abstract

We describe herein the discovery of a series of panaxytriol (PXT)-derived polyacetylene small molecules with promising cytoprotective activity. In mouse xenograft models, we have demonstrated the capacity of our synthetic analogs to mitigate a range of cancer therapeutic agent-induced toxicities, including body weight loss, lethality, neurotoxicity, and hematotoxicity. Our PXT analogs have also been found to reduce radiation-induced body weight loss and lethality in mouse models. Moreover, several PXT analogs appear to exhibit moderate in vivo antiinflammatory activity as well as in vitro immunoenhancing capabilities. These compounds appear to derive their activity through induction of cancer preventive phase 2 enzymes. The studies described herein suggest that coadministration of a PXT-derived agent with cancer chemotherapeutics or radiation therapy may serve to mitigate a range of therapy-associated toxicities.chemoprotective | neutraceutical

Phenyl dialkynylcarbinols, a Bioinspired Series of Synthetic Antitumor Acetylenic Lipids

“…These data are in full agreement with our previous results on non-aromatic DAC derivatives (see for instance entry 1, IC 50 0.09 μM vs entry 8, IC 50 3 μM and entry 2, IC 50 0.012 μM vs entry 9, IC 50 0.3 μM) . A similar gap in cytotoxicity in favor of the synthetic ( S )-configured carbinol compared to the naturally occurring ( R ) enantiomer has been observed for several acetylenic lipids issued from plants. ,, These observations suggest that the recently uncovered enantiospecific bioactivation mechanism of DACs may be shared by different types of LACs . A similar gap in cytotoxicity was observed between the two partially resolved samples of clickable PACs ( S )- and ( R )- 46 (entry 7, IC 50 0.28 μM vs entry 14, IC 50 1.8 μM), further confirming the relevance of 46 as a cellular probe.…”

Effect of variety, soil fertility status and agronomic treatments on carrot mineral and phytochemical composition and consumer liking of flavor traits

“…Unlike polyphenols which are widely available in most food crops, polyacetylenes are produced primarily in plant species used medicinally, such as ginseng and other plants in the Araliaceae family . Polyacetylenes are only produced in food crops from the Apiaceae family, including parsnip, fennel, carrot, celery and various herbs (parsley, dill, lovage).…”

Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview

“…These ginsenoside analogues have promising cytoprotective activities and can mitigate cancer treatmentrelated undesirable side-effects, including body weight loss, lethality, neurotoxicity, and hematotoxicity in mouse xenogra model. 164 inammatory activities and can induce cancer preventive Nrf2-dependent enzymes. 164 Hence, structurally modied ginsenosides could be used as adjuvant treatments to reduce toxic side effects and pain during chemotherapy.…”

“…164 inammatory activities and can induce cancer preventive Nrf2-dependent enzymes. 164 Hence, structurally modied ginsenosides could be used as adjuvant treatments to reduce toxic side effects and pain during chemotherapy.…”