Synthesis and Evaluation of 3'- and 4'-substituted Cyclohexyl Noviomimetics That Modulate Mitochondrial Respiration

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2022 Jul 29

PMID 35905686

Authors

Penchala Narasimharao Meka

Eva Amatya

Sukhmanjit Kaur

Monimoy Banerjee

Ang Zuo

Rick T Dobrowsky

Brian S J Blagg

Affiliations

Soon will be listed here.

Abstract

KU-32 (2) and KU-596 (3), are first and second generation cytoprotective novologues that are derivatives of novobiocin (1), a heat shock protein 90 (Hsp90) C-terminal inhibitor. Although 2 and 3 improve mitochondrial bioenergetics and have demonstrated considerable cytoprotective activity, they contain a synthetically demanding noviose sugar. This issue was initially addressed by creating noviomimetics, such as KU-1202 (4), which replaced the noviose sugar with ether-linked cyclohexyl derivatives that retained some cytoprotective potential due to their ability to increase mitochondrial bioenergetics. Based on structure-activity relationship (SAR) studies of KU-1202 (4), the current study investigated 3'- and 4'-substituted cyclohexyl scaffolds as noviomimetics and determined their efficacy at increasing mitochondrial bioenergetic as a marker for cytoprotective potential.

Citing Articles

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