Return to search

Synthesis of fluorinated heterocyclic compounds and study of their interaction with DNA

Over fifty structurally diverse, novel fluorinated heteroarenes, have been successfully synthesised by SNAr reaction of a range of fluorinated arenes including pentafluoropyridine, hexafluorobenzene, and methyl pentafluorobenzoate by introduction of a range of groups such as imidazole, triazole, benzimidazole, benzotriazole, and carbazole. Different water solubilising side chains were introduced to some of the successfully synthesised fluorinated heteroarenes to improve water solubility and potential biological activity. X-ray crystal structures of over 10 compounds were obtained including those of two macrocyclic compounds containing 21- and 24-membered rings. The synthesised compounds have been characterized by elemental analysis, IR, 1H and 19F spectroscopy and high resolution mass spectrometry. These compounds have been screened for their biological activities and possible interaction with DNA by methods including UV-visible spectroscopy, fluorescence spectroscopy, co-crystallization for X-ray diffraction analysis, and antimicrobial activity. A number of the fluoroaryl benzimidazole derivatives have been tested against K-562 and MCF-7 cell lines and G361 and HOS cell lines. From the all tested compounds three tethered fluoroaryl benzimidazole derivatives demonstrated micromolar inhibition against K-562 and MCF-7 cell lines. These compounds, in addition to 1-tetrafluoropyrid-4-yl-2-tetrafluoropyrid-4-ylsulfanyl-1H-benzimidazole, also demonstrated micromolar inhibition against G361 and HOS cell lines. Two of the compounds were found to activate caspases leading to apoptosis.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:719247
Date January 2017
CreatorsZeinali, Fatemeh
PublisherLoughborough University
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttps://dspace.lboro.ac.uk/2134/25150

Page generated in 0.0021 seconds