Synthesis, characterisation and antibacterial activity of new quinoline and quinoxaline hybrid molecules.
| dc.contributor.advisor | Koorbanally, Neil Anthony. | |
| dc.contributor.author | Sewpersad, Shirveen. | |
| dc.date.accessioned | 2023-10-31T07:00:59Z | |
| dc.date.available | 2023-10-31T07:00:59Z | |
| dc.date.created | 2018 | |
| dc.date.issued | 2018 | |
| dc.description | Doctoral Degree. University of KwaZulu-Natal, Durban. | en_US |
| dc.description.abstract | This thesis focussed on the synthesis of three series of hybrid molecules, all related to the quinoline or quinoxaline scaffolds. These are (i) 2-(1H-benzo[d]imidazol-2-yl)quinolines, (ii) quinoxaline-chalcones and their pyrazoline derivatives, and (iii) 5-(quinolin-2-ylmethylene)- 2-thioxothiazolidin-4-ones. The target molecules were fully characterized particularly by 2D NMR and verified by high resolution mass spectrometry. The synthesised compounds were tested for their antibacterial activity against two Gram +ve species, Staphylococcus aureus and MRSA and four Gram -ve bacteria, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Salmonella typhimurium to identify lead compounds which could be developed into active pharmaceutical ingredients for antibiotics. A total of fifty-six compounds were synthesised based on these scaffolds. The 2-(1H-benzo[d]imidazol-2-yl)quinolines were synthesised by the Doebner-Miller reaction of crotonaldehyde and substituted anilines, followed by oxidation and benzimidazole formation with o-phenylenediamine. The series of compounds consisted of 6- and 8- substituted halogen, methoxy and methyl groups. A complete structural elucidation of all compounds was carried out and the effects that the different substituents had on the resonances of the quinoline scaffold reported. The quinoxaline-chalcone and quinoxaline-chalcone-quinoline hybrids were synthesised from a quinoxaline acetophenone derivative and various 2- or 4- substituted benzaldehydes and 6- or 8- substituted quinoline-2-carbaldehydes via the Claisen-Schmidt condensation. These molecules were then converted to their respective pyrazoline derivatives using hydrazine hydrate. The 5-(quinolin-2-ylmethylene)-2-thioxothiazolidin-4-ones were synthesised from the Knoevenagel reaction of various 8- and 6-substituted quinoline-2- carbaldehydes and rhodanine. The method described is a convenient way to tag a rhodanine moeity onto a quinoline ring.Of the three sets of compounds synthesised, only the quinoxaline-chalcone-quinoline hybrids showed appreciable antibacterial activity, being active against the Gram +ve S. aureus and MRSA and not against the Gram -ve species, with the activity against S. aureus being much higher than that for MRSA. Quinoxaline chalcones showed no activity against the bacterial strains tested, however, when a quinoline moiety replaced the aromatic ring, eight derivatives showed enhanced antibacterial activity, having MBC values between 0.151-0.360 M against S. aureus and 10.9-618 M against MRSA. The quinoxaline-chalcone-quinoline hybrids showed antibacterial activity two orders of magnitude greater than ciprofloxacin and levofloxacin against S. aureus and comparable activity to these standards against MRSA. Interestingly, the 4'-Br and 4'-Cl pyrazoline derivatives of the quinoxaline chalcones (having MBC values of 11 and 12 M, respectively) showed comparable activity to levofloxacin and ciprofloxacin. | en_US |
| dc.identifier.uri | https://researchspace.ukzn.ac.za/handle/10413/22459 | |
| dc.language.iso | en | en_US |
| dc.subject.other | hybrid molecules. | en_US |
| dc.subject.other | MRSA. | en_US |
| dc.subject.other | Deuterated chloroform. | en_US |
| dc.title | Synthesis, characterisation and antibacterial activity of new quinoline and quinoxaline hybrid molecules. | en_US |
| dc.type | Thesis | en_US |