Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parasite-specific putrescine-N-acetyltransferase and polyamine oxidase, both involved in the reversed pathway of polyamine metabolism, were demonstrated for Ascaris suum and Onchocerca volvulus. Berenil-treatment was found to be correlated with accumulation of polyamines, especially spermine, obviously due to blockaded polyamine interconversion. Furthermore it was shown that added spermine to the culture medium led to the death of worms. These specificities might be exploited for chemotherapy of filarial infections. Polyamines are widely distributed in the nature. They are found in higher and lower eucaryotes and in procaryotes as well as in viruses (Tabor and Tabor, 1984). During the last years there have been many approaches to examine the role of polyamines in cell growth and differentiation in vertebrates (Tabor and Tabor, 1984; Pegg, 1986). The polyamine metabolism of parasites also has attracted increasing interest, e.g. in African trypanosomes the initial enzyme of polyamine synthesis - ornithine decarboxylase - has been exploited as a target for chemotherapy by using DFMO (DL alpha-difluoromethylornithine) (Bacchi et al., 1980; Bacchi et al., 1983; Fairlamb et al., 1985; Giffin et al., 1986). The polyamine metabolism of filaria and other helminths is still a neglected area of research, although there are reports about distribution pattern of polyamines and some peculiarities of polyamine metabolism in filarial worms (Srivastava et al., 1980; Wittich et al., 1987; Walter, 1988). DFMO and MGBG (methylglyoxal bis-(guanylhydrazone], both of which are potent inhibitors of polyamine synthesis in mammals, do not significantly effect the viability of filarial worms (Wittich et al., 1987).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The polyamine metabolism of filarial worms as chemotherapeutic target. 307 47

Polyamines are essential for cell growth and differentiation and therefore, S-adenosylmethionine decarboxylase (SAMDC), a key regulatory enzyme of the polyamine biosynthesis, is considered as a potentially important target for chemotherapy of filarial infections. Recombinant Onchocerca volvulus SAMDC was expressed in Escherichia coli and characterised. The enzyme activity was found to be stimulated 15-fold by addition of 1 mM putrescine. The Km-value for S-adenosylmethionine was determined to be 36 microM. Furthermore, the efficiencies of SAMDC inhibitors were analysed: Berenil inhibits the enzyme activity competitively with a Ki-value of 0.1 microM. MDL 73811 acts as an irreversible inhibitor with a Ki-value of 1.4 microM. Recently synthesised aromatic methylglyoxal bis(guanylhydrazone) analogues demonstrated high efficacy as inhibitors of the SAMDCs. Some of these analogues exhibited Ki-values of 5 and 14 nM for the Onchocerca enzyme, a result which shows an up to 100-fold increase in specificity compared to the value of 0.47 microM for methylglyoxal bis(guanylhydrazone). These inhibitors might have potential as drug candidates against filarial worms.
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PMID:MGBG analogues as potent inhibitors of S-adenosylmethionine decarboxylase of Onchocerca volvulus. 987 83