Kingianins O-Q: Pentacyclic polyketides from Endiandra kingiana as inhibitor of Mcl-1/Bid interaction

Fitoterapia
Mohamad Nurul AzmiKhalijah Awang

Abstract

A phytochemical study of the EtOAc-soluble part of the methanolic extract of the bark of Endiandra kingiana led to the isolation of three new pentacyclic kingianins as racemic mixtures, kingianins O-Q (1-3), together with the known kingianins A, F, K, L, M and N (4-9), respectively. The structures of the new kingianins 1-3 were determined by 1D and 2D NMR analysis in combination with HRESIMS experiments. Kingianins A-Q were assayed for Mcl-1 binding affinity. Kingianins G and H were found to be potent inhibitors of Mcl-1/Bid interaction. A structure-activity relationship study showed that potency is very sensitive to the substitution pattern on the pentacyclic core. In addition, in contrast with the binding affinity for Bcl-xL, the levorotatory enantiomers of kingianins G, H and J exhibited similar binding affinities for Mcl-1 than their dextrorotatory counterparts, indicating that the two anti-apoptotic proteins have slightly different binding profiles.

References

Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Apr 29, 2004·Analytical Biochemistry·Jie QianDavid J Burns
Aug 25, 2004·Analytical Biochemistry·Zaneta Nikolovska-ColeskaShaomeng Wang
Jul 20, 2006·Current Cancer Drug Targets·Hye Sook ChonJohn J Kavanagh
Dec 2, 2008·Nature Reviews. Drug Discovery·Guillaume LessenePeter M Colman
Feb 21, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Min H Kang, C Patrick Reynolds
Aug 14, 2010·Organic Letters·Aurélie LeverrierMarc Litaudon
May 10, 2011·Phytochemistry·Aurélie LeverrierMarc Litaudon
Jun 1, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matthew S Davids, Anthony Letai
May 22, 2013·Nature Chemical Biology·Paul S Jeng, Emily H Cheng
Feb 5, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamad Nurul AzmiKhalijah Awang

❮ Previous
Next ❯

Citations

Feb 10, 2020·Bioorganic & Medicinal Chemistry Letters·Shelly Gapil TiamasFanny Roussi
Jun 8, 2021·Chemical Science·Oussama YahiaouiThomas Fallon

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.