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New 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane thiosemicarbazones–thiocarbonohydrazones: cell growth inhibitory, antiviral and antimicrobial activity evaluation

2002; Elsevier BV; Volume: 12; Issue: 5 Linguagem: Inglês

10.1016/s0960-894x(01)00838-1

1464-3405

Antonios Kolocouris, Kostas Dimas, Christophe Pannecouque, Myriam Witvrouw, George B. Foscolos, George Stamatiou, George Fytas, Grigoris Zoidis, Nicolas Kolocouris, Graciela Andreï, Robert Snoeck, Erik De Clercq,

HIV/AIDS drug development and treatment

The new thiosemicarbazones and thiocarbonohydrazones Figure 1, Scheme 1 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 Figure 1, Scheme 1 inhibited tumor cell proliferation (GI50's range: 2.4–100 μM and mean GI50 43.9 μM against various human leukemic cell lines) while thiosemicarbazone Figure 1, Scheme 1 and thiocarbonohydrazone 5d exhibited significant inhibition of tumor cell proliferation (GI50's range 2.3–23.6 μM and mean GI50 7.2 μM for Figure 1, Scheme 1 and GI50's range 2.4–32.4 μM and mean GI50 12.8 μM for 5d). 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 4d, 5d against Gram-(+) bacteria (MIC50 117.3 and 133 μM, respectively). Using a combination of molecular mechanics calculations and NOE spectroscopy it was shown that the parent compounds Figure 1, Scheme 1 and Figure 1, Scheme 1 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.