Abstract
The biological evaluation of a natural sesquiterpene dimer meiogynin A 1, is described as well as that of five non-natural analogues. Although active on a micromolar range on the inhibition of Bcl-xL/Bak and Mcl-1/Bid interaction, meiogynin A 1 is not cytotoxic on three cell lines that overexpress Bcl-xL and Mcl-1. Contrarily, one of its analogues 6 with an inverted configuration on the side chain and an aromatic moiety replacing the cyclohexane ring was active on both target proteins, cytotoxic on a micromolar range and was found to induce apoptosis through a classical pathway.
Keywords:
Apoptosis; Bcl-xL; Mcl-1; Molecular docking; Sesquiterpene dimer.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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BH3 Interacting Domain Death Agonist Protein / antagonists & inhibitors
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BH3 Interacting Domain Death Agonist Protein / metabolism
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Benzoates / chemical synthesis
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Benzoates / chemistry*
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Benzoates / pharmacology
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Binding Sites
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Cell Line, Tumor
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Cell Survival / drug effects
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Humans
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Molecular Docking Simulation
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Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors
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Myeloid Cell Leukemia Sequence 1 Protein / metabolism*
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Naphthalenes / chemical synthesis
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Naphthalenes / chemistry*
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Naphthalenes / pharmacology
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Structure, Tertiary
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Sesquiterpenes / chemical synthesis
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Sesquiterpenes / chemistry*
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Sesquiterpenes / pharmacology
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bcl-2 Homologous Antagonist-Killer Protein / antagonists & inhibitors
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bcl-2 Homologous Antagonist-Killer Protein / metabolism
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bcl-X Protein / antagonists & inhibitors
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bcl-X Protein / metabolism*
Substances
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BH3 Interacting Domain Death Agonist Protein
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Benzoates
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Myeloid Cell Leukemia Sequence 1 Protein
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Naphthalenes
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Sesquiterpenes
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-X Protein
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meiogynin A
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Poly(ADP-ribose) Polymerases