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

The new thiosemicarbazones and thiocarbonohydrazones Figure 1 and 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 and Scheme 1 inhibited tumor cell proliferation (GI50ʹs range: 2.4–100 μM and mean GI50 43.9 μM against various human leukemic cell lines) while thiosemicarbazone Figure 1 and Scheme 1 and thiocarbonohydrazone 5d exhibited significant inhibition of tumor cell proliferation (GI50ʹs range 2.3–23.6 μM and mean GI50 7.2 μM for Figure 1 and Scheme 1 and GI50ʹs 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 TSCʹs 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 and Scheme 1 and Figure 1 and 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.