Bellany, F;
Tsuchiya, Y;
Tran, TM;
Chan, AWE;
Allan, H;
Gout, I;
Tabor, AB;
(2020)
Design and synthesis of Coenzyme A analogues as Aurora kinase A inhibitors: An exploration of the roles of the pyrophosphate and pantetheine moieties.
Bioorganic & Medicinal Chemistry
, 28
(22)
, Article 115740. 10.1016/j.bmc.2020.115740.
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Abstract
Coenzyme A (CoA) is a highly selective inhibitor of the mitotic regulatory enzyme Aurora A kinase, with a novel mode of action. Herein we report the design and synthesis of analogues of CoA as inhibitors of Aurora A kinase. We have designed and synthesised modified CoA structures as potential inhibitors, combining dicarbonyl mimics of the pyrophosphate group with a conserved adenosine headgroup and different length pantetheine-based tail groups. An analogue with a -SH group at the end of the pantotheinate tail showed the best IC50, probably due to the formation of a covalent bond with Aurora A kinase Cys290.
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