title: Synthesis and cytotoxicity of thieno[2,3-b]pyridine and furo[2,3-b]pyridine derivatives.
abstract: Forty seven thieno[2,3-b]pyridines-2-carboxamides, furo[2,3-b]pyridines-2-carboxamides and tetrahydrothieno[2,3-b]quinolones-2-carboxamides derivatives were synthesized and tested for their antiproliferative activity against the NCI-60 cell lines. The 5-keto-tetrahydrothieno[2,3-b]quinolones-2-carboxamides (series 17) were found to have the greatest activity, with the compound containing a 3-methoxyphenylcarboxamide (compound 17d) being the most active, with GI50 values in the low nanomolar range against a range of cell lines, in particular the melanoma cell line MDA-MD-435 (GI50 - 23 nM) and the breast cancer cell line MDA-MB-468 (GI50 - 46 nM). Molecular modelling of series 17 against phosphoinositide specific-phospholipase C reveals that the side chains of the amino acids His356, Glu341, Arg549 and Lys438 are involved in hydrogen bonding with the ligands as well as a lipophilic pocket is occupied by the phenyl carboxamide moiety.
authors.affiliation: School of Chemical Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Hung
authors.affiliation: School of Chemical Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Homayon J
authors.initials: HJ
authors.lastname: Arabshahi
authors.affiliation: Auckland Cancer Society Research Centre, The University of Auckland, New Zealand.
authors.forename: Euphemia
authors.initials: E
authors.lastname: Leung
authors.affiliation: School of Chemical Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Jóhannes
authors.initials: J
authors.lastname: Reynisson
authors.affiliation: School of Chemical Sciences, The University of Auckland, Auckland, New Zealand. Electronic address: d.barker@auckland.ac.nz.
authors.forename: David
authors.initials: D
authors.lastname: Barker
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D011725:Pyridines; D013876:Thiophenes; C584630:furo(3,2-b)pyridine
keywords: Furo[2,3-b]pyridines; Molecular modelling; Phosphoinositide specific-phospholipase C; Thieno[2,3-b]pyridines