Synthesis and biological activity of quinoline derivatives.

Abstract

A total of 42 compounds, which include 12 quinoline-3-carboxamides (A5a-l), 15 quinolone thiosemicarbazones (B5a-o) and 15 tetrazoloquinoline phenylhydrazones (C5a-o) were successfully synthesized and characterised. Of these 42 compounds, 36 have been prepared for the first time in this work, with 4 thiosemicarbazones and 2 phenylhydrazones being previously reported. The 2-chloroquinoline-3-carbaldehyde intermediate was the basic scaffold on which the three types of quinoline hybrids were based on. Various substituents were placed at C-6 on this substituent to create small libraries of compounds. This key intermediate was prepared using the Vilsmeier-Haack reaction, which resulted in a quinoline with a carbaldehyde at C-3. In the case of the quinoline-3-carboxamides, the aldehyde at position 3 was oxidized to the acid functionality via the Pinnick Oxidation. This was followed by the preparation of carboxamides using a coupling reaction with different substituted anilines and using the coupling reagents EDC∙HCl and HOBt in the presence of triethylamine used as a base. The thiosemicarbazones were prepared by condensing the 2-quinolone carbaldehydes with thiosemicarbazides and the tetrazolophenylhydrazones prepared by first forming a tetrazolo ring with sodium azide on the quinoline and then forming phenylhydrazones from the carbaldehyde moiety and phenylhydrazines. The quinoline scaffold was varied at C-6 with Cl, F, Br and CH3 groups and the various hybrids were varied again using different anilines, thiosemicarbazides and phenylhydrazines. The structures of the synthesised compounds were elucidated using 1D and 2D NMR spectroscopy. The synthesised compounds were tested for their antibacterial activity against two Gram positive (Staphylococcus aureus and S. aureus Rosenbach (MRSA)) and four Gram negative species, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Salmonella typhimurium. Although compounds in all three classes of hybrids showed antibacterial activity, these were not as good as current drugs being used as antibiotics. The synthesised compounds showed antibacterial activity in the range of 0.80 to 36.49 mM.