Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2375–2398 | Cite as

Design, synthesis, 3D pharmacophore, QSAR, and docking studies of some new (6-methoxy-2-naphthyl) propanamide derivatives with expected anti-bacterial activity as FABI inhibitor

  • Sally I. Eissa
  • Amel M. Farrag
  • Taghreed Z. Shawer
  • Yossry A. Ammar
Original Research
  • 157 Downloads

Abstract

Antibiotic resistance is a major health problem; so there is a emerging need for developing new antibiotic agents. A novel series of (6-methoxy-2-naphthyl) propanamide derivatives were synthesized and evaluated for their potential antibacterial activity. The minimum inhibitory concentration of these compounds were determined by microdilution technique against five known strains of bacteria. Test strains included three Gram-positive strains (Streptococcus pneumonia, Bacillus subtilis and Staphylococcus aureus) and two Gram-negative strains (Escherichia coli and Salmonella typhimurium). According to the observed antibacterial activity results showed that compounds N-(4-(2-(5-bromo-2-hydroxybenzylidene)hydrazine carbonyl) phenyl)-2-(6-meth oxynaphthalen-2-yl)propanamide 2d and N-(4-(2-(2,4-dichlorobenzylidene)hydrazine carbonyl)phenyl)-2-(6-methoxy-naphthalen-2-yl)propanamide 2j has potent antibacterial activity against B. subtilis (minimal inhibitory concentrations 1.95 µg/ml). Also 2-(6-methoxynaphthalen-2-yl)-N-(4-(2-(4-oxopentan-2-ylidene)hydrazinecarbonnyl)phenyl) propanamide 6 showed potent antibacterial activity against S. pneumonia (minimal inhibitory concentrations 1.95 µg/ml) compared to Naproxen (7.81, 15.63 µg/ml) and the reference drug Ampicillin (7.81 µg/ml). Two of the synthesized compounds, namely, 2j and 2k exhibited more potent antibacterial activity than the reference drugs (Gentamicin and Ampicillin) against all the test strains of bacteria. Molecular docking simulation was also carried out for Enoyl-aceyl carrier protein reductase enzyme, which is responsible for catalyzing the final step of bacterial fatty acid biosynthesis and is an attractive target for the development of novel antibacterial agents. In addition, generation of 3D pharmacophore model and quantitative structure–activity relationship models were combined to explore the structural requirements controlling the observed antibacterial properties.

Keywords

Naproxen Antibacterial Docking study 3D Pharmacophore QSAR 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Disclaimer

The authors alone are responsible for the content and writing of this article.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Sally I. Eissa
    • 1
  • Amel M. Farrag
    • 1
  • Taghreed Z. Shawer
    • 1
  • Yossry A. Ammar
    • 2
  1. 1.Pharmaceutical Chemistry Department, Faculty of PharmacyAl-Azher UniversityNasr CityEgypt
  2. 2.Organic Chemistry Department, Faculty of ScienceAl-Azher UniversityNasr CityEgypt

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