Adenosylmethionine decarboxylase inhibitors--lack of activity against cytopathic effects of HIV.
Many bis(amidinohydrazones) are potent inhibitors of adenosylmethionine decarboxylase (AdoMetDC), a key enzyme of polyamine biosynthesis, and some of them are also known to be powerful antiviral agents. Therefore, seven bis(amidinohydrazones), including the two most potent inhibitors of eukaryotic AdoMetDC so far reported, were screened for antiviral activity against the human immunodeficiency virus (HIV). The screening was performed by incubating susceptible human leukemia cells in microculture plates in the presence or absence of test compounds for 7 days and by determining the number of viable cells at the end of the test. None of the compounds screened, however, displayed any detectable antiviral activity (i.e. none of them increased the viability of virus-infected cells) in these tests whose aim was to reveal potential activity against the cytopathic effects of HIV. This result suggests that inhibitors of AdoMetDC, at least when used alone, are devoid of value for the prevention of the cytopathic effects of HIV. However, the possibility cannot be totally excluded that some of them might decrease the amount of infectious progeny viruses formed, just as methylglyoxal bis(amidinohydrazone) is known to do in the case of vaccinia virus.
Department of Chemistry, University of Helsinki, Finland.
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D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006678:HIV / Q000187:drug effects*; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
C051217:ethylmethylglyoxal bis(guanylhydrazone); C056522:diethylglyoxal bis(guanylhydrazone); D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone