title: New 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane thiosemicarbazones-thiocarbonohydrazones: cell growth inhibitory, antiviral and antimicrobial activity evaluation.
abstract: The new thiosemicarbazones and thiocarbonohydrazones derived from 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane were synthesized and evaluated for their inhibitory effect on tumor cell proliferation and their antiviral and antimicrobial activity. Thiosemicarbazone inhibited tumor cell proliferation (GI50's range: 2.4-100 microM and mean GI50 43.9 microM against various human leukemic cell lines) while thiosemicarbazone and thiocarbonohydrazone 5d exhibited significant inhibition of tumor cell proliferation (GI50's range 2.3-23.6 microM and mean GI50 7.2 microM for and GI50's range 2.4-32.4 microM and mean GI50 12.8microM for ). These GI50 values are comparable to that of 2-acetylpyridine thiosemicarbazone an important lead in TSC's family. The compounds did not afford specific activity against any of the viruses tested when examined at non-toxic concentrations. A weak activity was found for thiocarbonohydrazones against Gram-(+) bacteria (MIC(50) 117.3 and 133 microM, respectively). Using a combination of molecular mechanics calculations and NOE spectroscopy it was shown that the parent compounds and have opposite configuration around C=N bond. Whether this difference in structure can be correlated with the biological activity will be investigated in future studies.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771, Athens, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Kolocouris
authors.forename: Kostas
authors.initials: K
authors.lastname: Dimas
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: George B
authors.initials: GB
authors.lastname: Foscolos
authors.forename: George
authors.initials: G
authors.lastname: Stamatiou
authors.forename: George
authors.initials: G
authors.lastname: Fytas
authors.forename: Grigoris
authors.initials: G
authors.lastname: Zoidis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kolocouris
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D001419:Bacteria / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005562:Formazans; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014780:Viruses / Q000187:drug effects*
chemical_list: D005562:Formazans; D006835:Hydrazones; D013778:Tetrazolium Salts; D013882:Thiosemicarbazones; C079782:MTT formazan