Synthesis of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1, 4-dihydro-4-oxoquinoline-3-carboxylate derivatives and their biological evaluation. Issue 2 (15th January 2016)

• Record Type: Journal Article
• Authors: Venepally, Vijayendar; Prasad, R.B.N.; Poornachandra, Y.; Kumar, C. Ganesh; Jala, Ram Chandra Reddy
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 2(2016)
• Page Start: 613
• Page End: 617
• Publication Date: 2016-01-15
• Subjects: Cancer cell lines -- Carboxylated quinolones -- Lauric -- Myristic -- Cytotoxicity -- Antimicrobial -- Antioxidant -- Hexanoic acid; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.063
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1, 4-dihydro-4-oxoquinoline-3-carboxylate derivatives were prepared through multistep synthesis. The key step in the synthesis was to obtain the C-7 fatty amide derivative. The azide was selectively formed at C-7 position using sodium azide at 60 °C. Subsequently, the azide was reduced under mild conditions using zinc and ammonium chloride to form the corresponding amine. The synthesized derivatives were further subjected to biological evaluation studies like cytotoxicity against a panel of cancer cell lines such as DU145, A549, SKOV3, MCF7 and normal lung cells, IMR-90 as well as with antimicrobial and antioxidant activities. It was observed that the carboxylated quinolone derivatives with hexanoic (8a ), octanoic (8b ), lauric (8d ) and myristic (8e ) moieties exhibited promising cytotoxicity against all the tested cancer cell lines. The results also suggested that hexanoic acid-based fatty amide carboxylated quinolone derivative (8a ) exhibited promising activity against both bacterial and fungal strains and significant antibacterial activity was observed against Staphylococcus aureus MTCC 96 (MIC value of 3.9 μg/mL). The compound8a also showed excellent anti-biofilm activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121 with MIC values of 2.1 and 4.6 μg/mL, respectively.