Discovery of novel arylethenesulfonyl fluorides as potential candidates against methicillin-resistant of Staphylococcus aureus (MRSA) for overcoming multidrug resistance of bacterial infections

Gao Feng Zha, Shi Meng Wang, K. P. Rakesh, Bukhari Syed Nasir Abbas, H. M. Manukumar, H. K. Vivek, N. Mallesha, Hua Li Qin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The multidrug-resistant Staphylococcus aureus (MRSA) is one of the most prevalent human pathogens involved in many minor to major disease burdens throughout the world. Inhibition of biofilm formation is an attractive strategy to treat diseases associated with MRSA infection. In the present investigation, a series of functional group diverse (hetero)aryl fluorosulfonyl analogs were designed, synthesized and tested as antibacterial agents against Staphylococcal spp., and as anti-biofilm candidates. Compounds 8, 15, and 67 were found to possess potent in vitro antibacterial activity among this class of sulfonyl fluorides (MIC = 0.818 ± 0.42, 0.840 ± 0.37 and 0.811 ± 0.37 μg/mL respectively). The analogs 8, 15, 36, and 67 exhibited outstanding anti-biofilm properties compared to other available synthetic antibiotics. The efficacy of synthetic analogs displayed membrane-damaging effect and they are also validated by cellular content release assay. The insight physiological changes were explored by studying the intracellular redox activities through changing cyclic voltammetric (CV) method. The compounds 8, 15, 22, 32, 36, 51, and 67 were found to participate in the interfering in the electron transport chain (ETC) of MRSA. The analogs 8, 15, and 67 possess great potentiality for discovery and development of anti-staphylococcal drugs to treat the MRSA infections.

Original languageEnglish
Pages (from-to)364-377
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
DOIs
Publication statusPublished - 15 Jan 2019
Externally publishedYes

Fingerprint

Methicillin
Biofilms
Multiple Drug Resistance
Methicillin-Resistant Staphylococcus aureus
Fluorides
Bacterial Infections
Anti-Bacterial Agents
Pathogens
Electron Transport
Infection
Functional groups
Oxidation-Reduction
Staphylococcus aureus
Assays
Membranes
Pharmaceutical Preparations

Keywords

  • Antibacterial
  • Arylethenesulfonyl fluorides
  • Biofilm
  • Docking studies
  • Multidrug resistance

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Discovery of novel arylethenesulfonyl fluorides as potential candidates against methicillin-resistant of Staphylococcus aureus (MRSA) for overcoming multidrug resistance of bacterial infections. / Zha, Gao Feng; Wang, Shi Meng; Rakesh, K. P.; Syed Nasir Abbas, Bukhari; Manukumar, H. M.; Vivek, H. K.; Mallesha, N.; Qin, Hua Li.

In: European Journal of Medicinal Chemistry, 15.01.2019, p. 364-377.

Research output: Contribution to journalArticle

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