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)

Six new bimetallic complexes of the type CuCu, CuCo, CuNi, CuZn and CuMn were prepared. The structures of these complexes and the ligand have been proposed on the basis of FAB mass, elemental analysis, UV-vis, IR, EPR and CV studies. All the complexes completely cleave pBS (SK-) DNA at a concentration of 10 microM; however, even at lower concentrations of 2 microM and 0.1 microM, the complexes (I and Ia) showed partial cleavage. The results of the fluorescence binding studies of the metal complexes with CT-DNA showed that the presence of aliphatic ligands added additional binding effects including electrostatic, hydrogen binding and vander Waals interactions. Complexes (I, Ia) showed 50% inhibition of COX-1 and COX-2 activities at as low a concentration as 12.5 microM, 13.5 microM, 14 microM and 14.5 microM. Inhibition assay of top I and top II by different complexes in mutant yeast strains (JN394, JN394 t(-1) and JN394 t(2-5)) with all the complexes showed significant inhibition of topoisomerase at 5 microM concentration. Complexes I and Ia exhibited good anti-microbial activities against all human pathogens tested except Klebsiella pneumoniae. The following studies showed that among the synthesized bimetallic complexes, complexes I and Ia seem to be promising candidates possessing DNA cleavage activities besides anti-microbial and anti-inflammatory properties to serve as chemical nucleases and chemotherapeutic agents.
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PMID:Synthesis, characterization and in vitro biological activity studies of Cu-M (M = Cu2+, Co2+, Ni2+, Mn2+, Zn2+) bimetallic complexes. 1701 70

The synthesis of novel series of structurally related 4-pyrazolyl benzenesulfonamide derivatives is described. All the newly synthesized compounds were examined for their anti-inflammatory activity using cotton pellet induced granuloma and carrageenan induced rat paw edema bioassays. In addition the inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), ulcerogenic effect and acute toxicity were determined. Furthermore, all the compounds were evaluated for their in vitro antimicrobial activity against Eischerichia coli, Staphylococcus aureus and Candida albicans. Docking poses for compounds 6b and 7b separately in the active site of the human COX-2 enzyme and DNA-gyrase B were also obtained. The results revealed that compounds 3c, 4b, 4c, 5c, 6b and 7b exhibited comparable or better anti-inflammatory activity compared to indomethacin and celecoxib with no or minimal ulcerogenic effect and high safety margin. Compounds 3b, 3c, 4b, 4c, 5a-c, 6a, 6b and 7a-c displayed appreciable antibacterial activity against both E. coli and S. aureus compared with ampicillin. Compounds 5a-c and 7a had antibacterial activity against E. coli similar to ampicillin whereas compounds 3b, 3c, 4b, 4c, 6a and 7b displayed considerable activity against the microorganism. Compounds 3a, 3c, 4c, 5a-c, 6b and 7a-c had appreciable activity against S. aureus. Overall, compounds 4c, 6b and 7b are the most distinctive derivatives in the present study because of their remarkable anti-inflammatory potency and significant antibacterial activity. Furthermore, compounds 6b and 7b exhibited good selective inhibitory activity against COX-2 enzyme. Therefore, such compounds would represent a suitable template for the design of anti-inflammatory antimicrobial candidates with reasonable COX-2 selectivity.
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PMID:Synthesis and biological evaluation of novel pyrazole derivatives as anti-inflammatory antimicrobial agents. 1927 9

A molecular docking investigation has been carried out on cytotoxic prenylated flavonoids from Lonchocarpus haberi with cancer-relevant chemotherapeutic targets known to be inhibited by flavonoids. Two molecular docking programs, Molegro and ArgusDock, were used to compare the binding energies of Lonchocarpus flavonoids with other flavonoids, inhibitors, or known ligands, to aromatase (CYP 19), fatty acid synthase (FAS), xanthine oxidase (XO), cyclooxygenases (COX-1 and COX-2), lipoxygenase (LOX-3), ornithine decarboxylase (ODC), protein tyrosine kinase (PTK), phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), topoisomerase II (ATP binding site), ATP binding cassette (ABC) transporter, and phospholipase A(2) (PLA). The Lonchocarpus flavonoids examined in this study exhibited docking energies comparable to or stronger than other flavonoids that had been previously shown to be effective inhibitors of these enzymes. Furthermore, prenylated flavonoids, such as the Lonchocarpus flavonoids and xanthohumol, generally showed greater binding energies than the non-prenylated flavonoids. We conclude, therefore, that the Lonchocarpus flavonoids possibly owe their cytotoxic activity by inhibition of one or more of these enzymes.
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PMID:Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: a molecular docking analysis. 1960 3

The synthesis of a novel series of 4-thiazolylpyrazolyl derivatives is described in the present report. All the newly synthesized compounds were examined for their anti-inflammatory activity using cotton pellet-induced granuloma and carrageenan-induced rat paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), ulcerogenic effect and acute toxicity were also determined. Furthermore, all compounds were evaluated for their in vitro antimicrobial activity against Escherichia coli, Staphylococcus aureus and Candida albicans. A docking pose for compounds 8b, 10a and 10b separately in the active site of the human COX-2 enzyme and DNA-gyrase B was also obtained. The results revealed that compounds 8b, 10a and 10b exhibited good anti-inflammatory activity with no or minimal ulcerogenic effect and good safety margin. Compounds 10a and 10b were found to be the most potent anti-inflammatory agents in the present study. Meanwhile, 10a and 10b displayed higher selective inhibitory activity towards COX-2 compared to indomethacin. Moreover, compounds 10a and 10b exhibited promising antibacterial against both E. coli and S. aureus. Docking studies for 8b, 10a and 10b with COX-2 (PDB ID: 1CX2) and DNA-gyrase B (PDB ID: 1EI1) showed good binding profile.
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PMID:Synthesis and biological evaluation of some thiazolylpyrazole derivatives as dual anti-inflammatory antimicrobial agents. 2097 Feb 23