A Bisphenolic Honokiol Analog Outcompetes Oral Antimicrobial Agent Cetylpyridinium Chloride via a Membrane-Associated Mechanism

• Type of Material: Article
• Authors: Cristian Ochoa, University of Pennsylvania; Amy E. Solinski, Emory University; Marcus Nowlan, University of Pennsylvania; Madeline Dekarske, Emory University; William Wuest, Emory University; Marisa C. Kozlowski, University of Pennsylvania
• Language: English
• Date: 2020-01-01
• Publisher: AMER CHEMICAL SOC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2019
• Final Published Version (URL): http://dx.doi.org/10.1021/acsinfecdis.9b00190
• Title of Journal or Parent Work: ACS INFECTIOUS DISEASES
• Volume: 6
• Issue: 1
• Start Page: 74
• End Page: 79
• Grant/Funding Information: We are grateful to the NIH (GM112684, GM131902 [M.C.K.], DE025837 [W.M.W.]) and the NSF (CHE1764298[M.C.K.], CHE1755698 [W.M.W.]) for financial support of this research. Partial instrumentation support was provided by the NIH and NSF (1S10RR023444, 1S10RR022442, CHE 0840438, CHE-0848460, 1S10OD011980). C.O. acknowledges NIH training grant T32 GM071339. Dr. Charles W. Ross III is acknowledged for obtaining HRMS data. This research project was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core.
• Keywords: Pharmacology & Pharmacy; phenol; antibacterial; Life Sciences & Biomedicine; S. sanguini; DENTAL-CARIES; Infectious Diseases; STREPTOCOCCUS-MUTANS; BIOFILM; Science & Technology; S. gordonii; INSPIRED ANALOGS; MAGNOLOL; S. mutans; membrane; Chemistry, Medicinal
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Pharmacy; Chemistry, General

Abstract

Targeting Streptococcus mutans is the primary focus in reducing dental caries, one of the most common maladies in the world. Previously, our groups discovered a potent bactericidal biaryl compound that was inspired by the natural product honokiol. Herein, a structure activity relationship (SAR) study to ascertain structural motifs key to inhibition is outlined. Furthermore, mechanism studies show that bacterial membrane disruption is central to the bacterial growth inhibition. During this process, it was discovered that analog C2 demonstrated a 4-fold better therapeutic index compared to the commercially available antimicrobial cetylpyridinium chloride (CPC) making it a viable alternative for oral care.