Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of 21 compounds of trisubstituted pyrimidine derivatives have been synthesized and evaluated for their in vitro topoisomerase II inhibitory activity against filarial parasite Setaria cervi. Out of these, seven compounds (8, 11-14, 25 and 28) have shown 60-80% inhibition at 40 and 20 microg/mL concentration. Five compounds (12, 13, 14, 25 and 28) exhibited 70-80% inhibition at 10 microg/mL concentration and three compounds (13, 14 and 28) have shown 40-60% inhibition at 5 microg/mL concentration. All the above mentioned compounds have shown better topo II inhibitory activity than standard antifilarial drug (DEC) and enzyme topo II inhibitors (Novobiocin, Nalidixic acid).
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PMID:Syntheses of 2,4,6-trisubstituted pyrimidine derivatives as a new class of antifilarial topoisomerase II inhibitors. 1558 8

The antifilarial activity of two coumarin derivatives (A, B) and three glycosyl amine derivatives (D, E, F) was evaluated against a subperiodic strain of human lymphatic filarial parasite Brugia malayi by the intraperitoneal route at 50 mg/kg for 5 consecutive days. Of these, the two sugar derivatives (D and E) were selected for evaluation by the oral route based on their microfilaricidal (mild), macrofilaricidal and female worm sterilization efficacy using the i.p. route of administration. Compound E was finally selected for combination therapy on the basis of its microfilaricidal and embryostatic action by the oral route and its spectrum of activity against micro- and macrofilariae including embryostatic activity by the i.p. route. In addition, E also significantly inhibited the parasite DNA topoisomerase II. Compound A, in contrast, led to an enhanced adult worm burden. Compound B was toxic by the i.p. route, killing all of the treated animals before completion of the experiment. Some of these compounds demonstrated significant antifilarial efficacy of varying degree when tested in vitro Compounds B, D and F also killed adult B. malayi in vitro at 100 muM while 50 muM resulted in very slow motility of worms. Compound E in combination with a promising macrofilaricidal benzopyran derivative reported by us recently (compound C) did not show any synergistic or additive effect. These two compounds (C and E) individually on oral administration with either DEC or ivermectin significantly improved microfilaricidal efficacy in terms of intensity and duration of suppressed microfilaraemia. The combination of DEC with compound E demonstrated marginal enhancement in adulticidal efficacy, however, the embryostatic effect of the duo was significantly higher than that exerted by the individual agents. It may thus be inferred that in the absence of an adulticidal antifilarial drug, the use of potential antifilarials in combination with the standard filaricides may yield better results.
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PMID:Search for new prototypes for the chemotherapy of filariasis: a chemotherapeutic and biochemical approach. 1573 72

A novel series of 4-amino-5-cyano-2, 6-disubstituted pyrimidines have been synthesized and evaluated for their in vitro antifilarial DNA topoisomerase II activity against filarial parasite Setaria Cervi. In particular compounds bearing 4-chloro-phenyl substitutent at position-6, exhibited strong inhibition at 40 microg/mL and 5 microg/mL concentration. The present study based on the biological results obtained, suggests that the nature of substitutent at position-4 in the phenyl ring directly affects DNA topoisomerase II inhibitory activity. Most of the compounds have shown better topoisomerase II inhibitory activity than the standard antifilarial drug (DEC) and the topoisomerase II inhibitors (Novobiocin, Nalidixic acid).
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PMID:Synthesis of 4-amino-5-cyano-2, 6-disubstituted pyrimidines as a potential antifilarial DNA topoisomerase II inhibitors. 1899 43