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

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	393-397
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	11
Issue number	3
DOIs	https://doi.org/10.1021/acsmedchemlett.9b00159
State	Published - 12 Mar 2020

Bibliographical note

Funding Information:
This work was funded by the National Institute of General Medical Sciences (GM119426) and the Georgia Research Alliance based in Atlanta, Georgia to W.M.W., and by National Institutes of Health grant P01 AI083214 to E.M. The NMR instruments used in this work were supported by the National Science Foundation (CHE1531620).

Publisher Copyright:
© 2019 American Chemical Society.

Keywords

CD437
Methicillin resistant Staphylococcus aureus
cancer
persister
retinoid

Access to Document

10.1021/acsmedchemlett.9b00159

Cite this

@article{984f5a9e515e49aaac6eccc2650d1a52,

title = "Structure-Activity Relationship and Anticancer Profile of Second-Generation Anti-MRSA Synthetic Retinoids",

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.",

keywords = "CD437, Methicillin resistant Staphylococcus aureus, cancer, persister, retinoid",

author = "Cheng, {Ana V.} and Wooseong Kim and Escobar, {Iliana E.} and Eleftherios Mylonakis and Wuest, {William M.}",

note = "Funding Information: This work was funded by the National Institute of General Medical Sciences (GM119426) and the Georgia Research Alliance based in Atlanta, Georgia to W.M.W., and by National Institutes of Health grant P01 AI083214 to E.M. The NMR instruments used in this work were supported by the National Science Foundation (CHE1531620). Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

year = "2020",

month = mar,

day = "12",

doi = "10.1021/acsmedchemlett.9b00159",

language = "English",

volume = "11",

pages = "393--397",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

number = "3",

}

TY - JOUR

T1 - Structure-Activity Relationship and Anticancer Profile of Second-Generation Anti-MRSA Synthetic Retinoids

AU - Cheng, Ana V.

AU - Kim, Wooseong

AU - Escobar, Iliana E.

AU - Mylonakis, Eleftherios

AU - Wuest, William M.

N1 - Funding Information: This work was funded by the National Institute of General Medical Sciences (GM119426) and the Georgia Research Alliance based in Atlanta, Georgia to W.M.W., and by National Institutes of Health grant P01 AI083214 to E.M. The NMR instruments used in this work were supported by the National Science Foundation (CHE1531620). Publisher Copyright: © 2019 American Chemical Society.

PY - 2020/3/12

Y1 - 2020/3/12

N2 - 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.

AB - 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.

KW - CD437

KW - Methicillin resistant Staphylococcus aureus

KW - cancer

KW - persister

KW - retinoid

UR - http://www.scopus.com/inward/record.url?scp=85081886609&partnerID=8YFLogxK

U2 - 10.1021/acsmedchemlett.9b00159

DO - 10.1021/acsmedchemlett.9b00159

M3 - Article

AN - SCOPUS:85081886609

SN - 1948-5875

VL - 11

SP - 393

EP - 397

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this