Heterocyclic thiosemicarbazones: correlation between structure, inhibition of ribonucleotide reductase, and inhibition of DNA viruses.
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The effectiveness of chalkones and derivatives as antibacterial and antifungal agents stimulated our interest in the possibility of coupling this type of compound with certain hydrazines and thiosemicarbazides to determine the potential chemotherapeutic activity of these combinations as anticancer and antimalarial agents. Accordingly, 18 hydrazine and thiosemicarbazide derivatives of alpha-methylchalkone (dypnone) have been synthesized for study as potential antitumor agents in animal tumor systems against Walker 256 carcinosarcoma (intramuscular) and leukemia L-1210 and for antimalarial activity against Plasmodium berghei in experimentally infected mice. Of the series of chalkone derivatives, significant inhibition in preliminary tests against the Walker 256 carcinosarcoma (intramuscular) rat tumor system was exhibited by alpha-methylchalkone-1,4-phthalazinediyldihydrazone and showed activity in the leukemia 1210 mouse tumor system. The guanylhydrazone of alpha-methylchalkone showed good inhibition with confirmed activity against Plasmodium berghei in experimentally infected mice.
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Direct immunofluorescence supplied evidence of the antiviral action of a new synthetic derivative (5-sulfamido-ITSC) against vaccina virus in HeLa cell cultures. The antiviral potential of the new derivative is expressed by a 10-18 delay in the appearance of the viral antigen and by the quantitative reduction of synthesis. Administered in a single dose of 40 uM/ml, after infection of the HeLa cells, 5-sulfamido-ITSC does not arrest the infection and bring about elimination of the virus from the cell, in the course of a single viral multiplication cycle. Direct immunofluorescence is a rapid, specific method for detection of the in vitro antiviral action of synthetic derivatives.
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