Synthesis and biological activity of quinoline derivatives.
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Date
2018
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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.
Description
Doctoral Degree. University of KwaZulu-Natal, Durban.