55489-15-1Relevant articles and documents
The giardicidal activity of lobendazole, fabomotizole, tenatoprazole and ipriflavone: A ligand-based virtual screening and in vitro study
Pérez-Villanueva, Jaime,Yépez-Mulia, Lilián,Rodríguez-Villar, Karen,Cortés-Benítez, Francisco,Palacios-Espinosa, Juan Francisco,Soria-Arteche, Olivia
, (2020/12/29)
A ligand-based virtual screening study to search for giardicidal compounds on a 6551 ChEMBL drugs database was carried out using molecular similarity. Three fingerprints implemented in MayaChemTools with different design and validated by ROC curves, were used. Twelve compounds were retrieved from this screening, from which, four representative compounds were selected to carry out biological assays. Whereas two compounds were commercially available, the additional two compounds were synthesized during the development of this work. The biological assays revealed that the compounds possess in vitro activity against five strains of Giardia intestinalis, each with different susceptibility/resistance rates to metronidazole, albendazole and nitazoxanide. Particularly, tenatoprazole showed the best effect against the WB and IMSS strains. Furthermore, fabomotizole, tenatoprazole and ipriflavone showed a higher activity against resistant strains than the reference drugs: metronidazole, albendazole and nitazoxanide.
Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
, p. 6289 - 6304 (2017/08/02)
PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
METHOD OF USING (H+/K+)ATPASE INHIBITORS AS ANTIVIRAL AGENTS
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, (2008/06/13)
A class of compounds which are (H+/K+) ATPase inhibitors can be used for the treatment of viral infections. Compounds of particular interest are defined by Formula III: wherein D is N or CH; wherein R7 is one or more radicals selected from hydrido, alkoxy, amino, cyano, nitro, hydroxyl, alkyl, halo, haloalkyl, carboxyl, alkanoyl, nitro, amino, alkylamino, aminocarbonyl , aminosulfonyl , alkylaminocarbonyl, alkylcarbonylamino, alkoxycarbonyl, alkylaminosulfonyl, alkylsulfonylamino, alkylthio, alkyl-sulfinyl and alkylsulfonyl; wherein R8 is selected from hydrido, alkyl and cycloalkyl; wherein R9 is one or more radicals selected from hydrido, alkoxy, amino, alkyl, halo, cyano, nitro, hydroxyl, haloalkyl, nitro, carboxyl, alkanoyl, amino, alkylamino, dialkylamino, aminocarbonyl , alkylaminocarbonyl, alkylcarbonylamino, aminosulfonyl, alkylaminosulfonyl, alkylsulfonylamino, alkoxycarbonyl, alkylthio, alkylsulfinyl and alkylsulfonyl; and wherein R10 and R11 are independently selected from hydrido, alkyl, aryl, alkylcarbonyl and arylcarbonyl wherein the aryl ring may be further substituted with one or more radicals selected from alkyl, halo, hydrazidylcarbonyl, aminocarbonyl and alkoxy; or wherein R10 and R11 together with the nitrogen atom form a heterocyclic ring
