title: Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety.
abstract: Identification of the novel (E)-N'-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19-26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G₁ cell cycle arrest, as well as upregulation of the p27(kip1) cell cycle regulating protein.
authors.affiliation: School of Chemistry, The University of New South Wales Australia, Sydney, NSW 2052, Australia. muratbingul1983@gmail.com.|Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia. muratbingul1983@gmail.com.
authors.forename: Murat
authors.initials: M
authors.lastname: Bingul
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia. Otan@ccia.unsw.edu.au.
authors.forename: Owen
authors.initials: O
authors.lastname: Tan
authors.affiliation: School of Chemistry, The University of New South Wales Australia, Sydney, NSW 2052, Australia. z3217087@gmail.com.|Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia. z3217087@gmail.com.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gardner
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia. ssutton@ccia.unsw.edu.au.
authors.forename: Selina K
authors.initials: SK
authors.lastname: Sutton
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia. garndt@ccia.unsw.edu.au.|ACRF Drug Discovery Centre for Childhood Cancer, Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2052, Australia. garndt@ccia.unsw.edu.au.
authors.forename: Greg M
authors.initials: GM
authors.lastname: Arndt
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia. gmarshall@ccia.unsw.edu.au.|Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW 2031, Australia. gmarshall@ccia.unsw.edu.au.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Marshall
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, The University of New South Wales Australia, Sydney, NSW 2031, Australia. bcheung@ccia.unsw.edu.au.
authors.forename: Belamy B
authors.initials: BB
authors.lastname: Cheung
authors.affiliation: School of Chemistry, The University of New South Wales Australia, Sydney, NSW 2052, Australia. n.kumar@unsw.edu.au.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
authors.affiliation: School of Chemistry, The University of New South Wales Australia, Sydney, NSW 2052, Australia. d.black@unsw.edu.au.
authors.forename: David StC
authors.initials: DS
authors.lastname: Black
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006835:Hydrazones / Q000737:chemistry; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006834:Hydrazines; D006835:Hydrazones; D011804:Quinolines
keywords: anticancer; breast cancer; hydrazide-hydrazone; neuroblastoma; quinoline