New 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane thiosemicarbazones-thiocarbonohydrazones: cell growth inhibitory, antiviral and antimicrobial activity evaluation.
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.
Kolocouris
Antonios
A
School of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771, Athens, Greece.
Dimas
Kostas
K
Pannecouque
Christophe
C
Witvrouw
Myriam
M
Foscolos
George B
GB
Stamatiou
George
G
Fytas
George
G
Zoidis
Grigoris
G
Kolocouris
Nicolas
N
Andrei
Graciela
G
Snoeck
Robert
R
De Clercq
Erik
E
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*
D005562:Formazans; D006835:Hydrazones; D013778:Tetrazolium Salts; D013882:Thiosemicarbazones; C079782:MTT formazan