Structure-Activity Relationship and Anticancer Profile of Second-Generation Anti-MRSA Synthetic Retinoids

Ana V Cheng; Wooseong Kim; Iliana E Escobar; Eleftherios Mylonakis; William M Wuest

doi:10.1021/acsmedchemlett.9b00159

Structure-Activity Relationship and Anticancer Profile of Second-Generation Anti-MRSA Synthetic Retinoids

ACS Med Chem Lett. 2019 Jul 17;11(3):393-397. doi: 10.1021/acsmedchemlett.9b00159. eCollection 2020 Mar 12.

Authors

Ana V Cheng¹, Wooseong Kim², Iliana E Escobar², Eleftherios Mylonakis², William M Wuest^{1

3}

Affiliations

¹ Department of Chemistry, Emory University, Atlanta, Georgia 30322 United States.
² Division of Infectious Diseases, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903 United States.
³ Emory Antibiotic Resistance Center, Emory School of Medicine, Emory University, Atlanta, Georgia 30322, United States.

Abstract

We previously reported the antibacterial activity of CD437, a known antitumor compound. It proved to be a potent antimicrobial agent effective against both growing and persister cells of methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report the synthesis of a panel of analogs and their effect on both MRSA and cancer cells. The hydrophobic group of the parent compound was varied in steric bulk, and lipid-mimicking analogs were tested. Biological assessment confirmed that the adamantane moiety is the most effective substitution for antibacterial activity, and some preferential action in cancer over MRSA was achieved.

Abstract

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