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dc.contributor.authorDelfosse, Pierre
dc.contributor.authorSeaton, Colin C.
dc.contributor.authorMale, L.
dc.contributor.authorLord, Rianne M.
dc.contributor.authorPike, Sarah J.
dc.date.accessioned2021-12-09T14:54:04Z
dc.date.accessioned2021-12-20T14:02:21Z
dc.date.available2021-12-09T14:54:04Z
dc.date.available2021-12-20T14:02:21Z
dc.date.issued2021-06-30
dc.identifier.citationDelfosse P, Seaton CC, Male L et al (2021) Influence of Terminal Functionality on the Crystal Packing Behaviour and Cytotoxicity of Aromatic Oligoamides. Frontiers in Chemistry. 9: 709161.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18688
dc.descriptionYesen_US
dc.description.abstractThe synthesis and characterization of three aromatic oligoamides, constructed from the same pyridyl carboxamide core but incorporating distinct end groups of acetyl (Ac) 1, tert-butyloxycarbonyl (Boc) 2 and amine 3 is reported. Single crystal X-ray diffraction analysis of 1-3 and a dimethylsulfoxide (DMSO) solvate of 2 (2-DMSO), has identified the presence of a range of intra- and intermolecular interactions including N-H⋯N, N-H⋯O=C and N-H⋯O=S(CH3)2 hydrogen-bonding interactions, C-H⋯π interactions and off-set, face-to-face stacking π-π interactions that support the variety of slipped stack, herringbone and cofacial crystal packing arrangements observed in 1-3. Additionally, the cytotoxicity of this series of aromatic oligoamides was assessed against two human ovarian (A2780 and A2780cisR), two human breast (MCF-7 and MDA-MB-231) cancerous cell lines and one non-malignant human epithelial cell line (PNT-2), to investigate the influence of the terminal functionality of these aromatic oligoamides on their biological activity. The chemosensitivity results highlight that modification of the terminal group from Ac to Boc in 1 and 2 leads to a 3-fold increase in antiproliferative activity against the cisplatin-sensitive ovarian carcinoma cell line, A2780. The presence of the amine termini in 3 gave the only member of the series to display activity against the cisplatin-resistance ovarian carcinoma cell line, A2780cisR. Compound 2 is the lead candidate of this series, displaying high selectivity towards A2780 cancer cells when compared to non-malignant PNT-2 cells, with a selectivity index value >4.2. Importantly, this compound is more selective towards A2780 (cf. PNT-2) than the clinical platinum drugs oxaliplatin by > 2.6-fold and carboplatin by > 1.6-fold.en_US
dc.description.sponsorshipUniversity of Bradford Development Fund; University of Birmingham - Birmingham Fellowship; UKRI Future Leaders Fellowship (MR/T041315/1); UKRI Future Leaders Fellowship (MR/S035486/2)en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.3389/fchem.2021.709161en_US
dc.rights(c) 2021 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/)en_US
dc.subjectAromatic oligoamidesen_US
dc.subjectCytotoxicityen_US
dc.subjectCrystallographyen_US
dc.subjectTerminal groupen_US
dc.subjectBrest canceren_US
dc.subjectOvarian canceren_US
dc.titleInfluence of Terminal Functionality on the Crystal Packing Behaviour and Cytotoxicity of Aromatic Oligoamidesen_US
dc.status.refereedYesen_US
dc.date.Accepted2021-06-10
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.date.updated2021-12-09T14:54:05Z
refterms.dateFOA2021-12-20T14:02:40Z
dc.openaccess.statusGolden_US


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