Inhibition of CDK2/CyclinE1 by xanthones from the mangosteen (Garcinia mangostana): a structure-activity relationship study.

Natural Product Research
Mirielle C NaumanJeremy J Johnson

Abstract

Uncontrolled regulation of cyclin dependent kinases (CDKs) has negative implications in many cancers and malignancies and has recently led to the approval of select CDK inhibitors. Herein we present data reporting that xanthones, a class of compounds isolated from the purple mangosteen (Garcinia mangostana) fruit, can inhibit CDK2/CyclinE1. We evaluated nine different xanthones, including α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinone C, garcinone D, 9-hydroxycalabaxanthone, and 3-isomangostin for toxicity in 22Rν1 (prostate cancer cells) and MDA-MB-231 (breast cancer cells). All compounds dose-dependently inhibited the viability of both cell lines. A cell free biochemical assay was performed to determine if selected phytochemicals inhibited CDK2/CyclinE1. γ-Mangostin and α-mangostin were the strongest inhibitors, respectively. The results suggest that the position of key functional groups including hydroxyl and isoprenyl groups contribute to the CDK2 inhibitory effect. Taken together, the evidence suggests that xanthones can directly target CDK2 providing a possible explanation for their therapeutic potential.

References

Mar 21, 2002·Nature Reviews. Cancer·M Malumbres, M Barbacid
Aug 30, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·José Pedraza-ChaverriJazmin M Pérez-Rojas
Nov 13, 2012·Current Drug Targets·Atulkumar RamaiyaJeremy J Johnson
Jun 28, 2013·Frontiers in Pharmacology·Gongbo LiJeremy J Johnson
Oct 6, 2016·Oxidative Medicine and Cellular Longevity·Wichit SuthammarakWeerasak Muangpaisan
Jan 28, 2017·Nature Reviews. Cancer·Tobias Otto, Piotr Sicinski
Feb 9, 2017·Pharmacology & Therapeutics·Steven R WhittakerPaul A Clarke
Mar 8, 2018·Natural Product Research·Sabrin R M IbrahimGamal A Mohamed
Aug 18, 2018·International Journal of Molecular Sciences·Yunfeng ZhengKarl Wah Keung Tsim
Nov 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agnieszka BartmańskaJoanna Wietrzyk

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