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Review
. 2024 Jun 1;25(11):6099.
doi: 10.3390/ijms25116099.

Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?

Celia María Curieses Andrés  1 , José Manuel Pérez de la Lastra  2 , Elena Bustamante Munguira  1 , Celia Andrés Juan  3 , Eduardo Pérez-Lebeña  4
Affiliations
Review

Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?

Celia María Curieses Andrés et al. Int J Mol Sci. .

Abstract

Michael acceptors represent a class of compounds with potential anti-cancer properties. They act by binding to nucleophilic sites in biological molecules, thereby disrupting cancer cell function and inducing cell death. This mode of action, as well as their ability to be modified and targeted, makes them a promising avenue for advancing cancer therapy. We are investigating the molecular mechanisms underlying Michael acceptors and their interactions with cancer cells, in particular their ability to interfere with cellular processes and induce apoptosis. The anti-cancer properties of Michael acceptors are not accidental but are due to their chemical structure and reactivity. The electrophilic nature of these compounds allows them to selectively target nucleophilic residues on disease-associated proteins, resulting in significant therapeutic benefits and minimal toxicity in various diseases. This opens up new perspectives for the development of more effective and precise cancer drugs. Nevertheless, further studies are essential to fully understand the impact of our discoveries and translate them into clinical practice.

Keywords: Michael acceptor compounds; chemotherapy; neoplastic metabolism.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Michael reaction utilizing different (pro-)nucleophiles.
Figure 2
Figure 2
Michael acceptor groups.
Figure 3
Figure 3
Michael donor groups.
Figure 4
Figure 4
MA reaction with the thiol group of cysteines in Keap1 protein.
Figure 5
Figure 5
Mechanism of reversible and irreversible covalent inhibitors.
Figure 6
Figure 6
Mechanism of reversible inhibition by conjugate addition to cyano acrylamides.
Figure 7
Figure 7
Mechanism of irreversible inhibition by conjugate addition to acrylamides.
Figure 8
Figure 8
Molecular structures of tyrosine kinase inhibitors.
Figure 9
Figure 9
Molecular structures of CDK inhibitors.
Figure 10
Figure 10
Molecular structure of Hesperadin.
Figure 11
Figure 11
Molecular structures of BTK inhibitors.
Figure 12
Figure 12
Endogenous nitration of UFAs.
Figure 13
Figure 13
NO2-FAs reaction with the thiol group of biologically relevant proteins.
Figure 14
Figure 14
Molecular structures of anthracyclines.
Figure 15
Figure 15
Molecular structures of SINEs.
Figure 16
Figure 16
Piperlongumine and piperine molecular structure.
Figure 17
Figure 17
Sinomenine molecular structure.
Figure 18
Figure 18
Zerumbone and Eupalinolide J molecular structure.
Figure 19
Figure 19
Yuanhuacine molecular structure.
Figure 20
Figure 20
Celastrol molecular structure.
Figure 21
Figure 21
Physalin A molecular structure.
Figure 22
Figure 22
Withaferin A molecular structure.
Figure 23
Figure 23
Glycyrrhizinic acid molecular structure.
Figure 24
Figure 24
Fucoxanthin molecular structure.
Figure 25
Figure 25
Astaxanthin molecular structure.
Figure 26
Figure 26
Bioactivity of ASX.
Figure 27
Figure 27
α-acids and β-acids molecular structures.
Figure 28
Figure 28
Molecular structures of Annonacin, Annonin, Bullatacin and Uvaricin.
Figure 29
Figure 29
Leptomycin B molecular structure.
Figure 30
Figure 30
Molecular structure of CAPE, DA, CGA and RA.
Figure 31
Figure 31
Trans and cis isomers of the basic chalcone skeleton.
Figure 32
Figure 32
Molecular structure of Xanthohumol, Brussochalcone A, Brussochalcone B and Licochalcone A.
Figure 33
Figure 33
Molecular structure of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin.
Figure 34
Figure 34
Tautomerism of curcumin.
Figure 35
Figure 35
Michael acceptor moieties in flavonoids.
Figure 36
Figure 36
Flavones in Scutellaria baicalensis extract.
Figure 37
Figure 37
Coumarin structure.
Figure 38
Figure 38
Classification of coumarins according to their chemical structure.
Figure 39
Figure 39
Chemical structures of Esculetin, Grandivitine, Agasiline and Aegelinol benzoate.
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