Discovery of novel halogenated 8-hydroxyquinoline-based anti-MRSA agents: In vitro and QSAR studies

Rungrot Cherdtrakulkiat; Apilak Worachartcheewan; Srisurang Tantimavanich; Ratana Lawung; Nujarin Sinthupoom; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul

doi:10.1002/ddr.21611

Discovery of novel halogenated 8-hydroxyquinoline-based anti-MRSA agents: In vitro and QSAR studies

Drug Dev Res. 2020 Feb;81(1):127-135. doi: 10.1002/ddr.21611. Epub 2019 Oct 16.

Authors

Rungrot Cherdtrakulkiat¹, Apilak Worachartcheewan^{2

3}, Srisurang Tantimavanich¹, Ratana Lawung¹, Nujarin Sinthupoom¹, Supaluk Prachayasittikul⁴, Somsak Ruchirawat^{5

6

7}, Virapong Prachayasittikul¹

Affiliations

¹ Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
² Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
³ Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
⁴ Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
⁵ Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok, Thailand.
⁶ Program in Chemical Biology, Chulabhorn Graduate Institute, Bangkok, Thailand.
⁷ Center of Excellence on Environmental Health and Toxicology, Commission on Higher Education (CHE), Ministry of Education, Thailand.

PMID: 31617606
DOI: 10.1002/ddr.21611

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infection has been considered to be one of global health problems due to limited classes of effective antimicrobial drugs. Herein, 8-hydroxyquinoline (8HQ) and its derivatives (1-7) were investigated for their anti-MRSA and antioxidant activities. Cloxyquin (2), a halogenated 8HQ, exerted the highest antimicrobial activity (MIC₅₀ ≤ 5.57 μM) with high safety index, whereas an amino-derivative 7 showed the strongest antioxidant activity. Additionally, quantitative structure-activity relationship (QSAR) study demonstrated that mass, polarizability, topological charge, and van der Waals volume are essential properties governing the anti-MRSA activity. Taken together, cloxyquin was highlighted as a promising compound for further development as a novel anti-MRSA agent. QSAR findings would also benefit for further rational design of novel 8HQ-based compounds to combat the MRSA resistance.

Keywords: 8-hydroxyquinoline; QSAR; antimicrobial activity; antioxidant activity; cloxyquin; methicillin-resistant Staphylococcus aureus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chloroquinolinols / chemical synthesis*
Chloroquinolinols / chemistry
Chloroquinolinols / pharmacology
Drug Design
Halogens / chemistry
Methicillin-Resistant Staphylococcus aureus / drug effects*
Microbial Sensitivity Tests
Molecular Structure
Oxyquinoline / chemistry*
Quantitative Structure-Activity Relationship

Substances

Chloroquinolinols
Halogens
Oxyquinoline
cloxyquin