The Michael addition reaction is a type of nucleophilic conjugate addition where a nucleophile attacks an α,β-unsaturated carbonyl compound (or, more generally, an electron-deficient alkene). This reaction is a cornerstone in organic synthesis, allowing the formation of carbon–carbon or carbon–heteroatom bonds under relatively mild conditions.
-In biological systems, proteins often contain cysteine residues with thiol (-SH) groups that can act as nucleophiles.
Some anticancer drug development strategies employ compounds that act as Michael acceptors. These drugs are designed to specifically form covalent bonds with cysteine residues on target proteins (such as enzymes or receptors involved in cancer cell survival). The irreversible binding can result in a prolonged inhibitory effect.
Nrf2 Pathway Activation: Certain natural compounds with Michael acceptor properties (such as curcumin or specific electrophilic phytochemicals) can activate the Nrf2 (nuclear factor erythroid 2–related factor 2) pathway.
-The modulation of proteins via Michael addition can indirectly affect the cellular redox state, influencing ROS levels.
Natural compounds known to exhibit Michael acceptor properties:
-Curcumin
-Sulforaphane
-Parthenolide
-Caffeic Acid Phenethyl Ester (CAPE)
-Withania somnifera (ashwagandha)
-Gambogic Acid
-Dimethyl Fumarate (DMF) (resembles natural fumaric acid)
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