Literature summary for 3.4.22.B62 extracted from

Ferraro, F.; Merlino, A.; Gil, J.; Cerecetto, H.; Corvo, I.; Cabrera, M.
Cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-oxide derivatives (2019), Molecules, 24, 2348 .

Search for more literature for 3.4.22.B62

Inhibitors

Inhibitors	Comment	Organism
(2E)-2-[(2,3-dimethyl-1,4-dioxidoquinoxalin-6-yl)methylidene]-N-(2-phenylethyl)hydrazinecarboxamide	32% inhibiton at 0.01 mM	Fasciola hepatica
(2E)-2-[(2-amino-3-cyano-1,4-dioxidoquinoxalin-6-yl)methylidene]-N-(2-phenylethyl)hydrazinecarboxamide	61% inhibiton at 0.01 mM	Fasciola hepatica
(2E)-2-[(2-amino-3-cyano-1,4-dioxidoquinoxalin-6-yl)methylidene]-N-(prop-2-en-1-yl)hydrazinecarbothioamide	39% inhibiton at 0.01 mM	Fasciola hepatica
(2E)-2-[(2-amino-3-cyano-1,4-dioxidoquinoxalin-6-yl)methylidene]-N-butylhydrazinecarboxamide	27% inhibiton at 0.01 mM	Fasciola hepatica
(2Z)-2-[(2E)-[(2,3-dimethyl-1,4-dioxidoquinoxalin-6-yl)methylidene]hydrazinylidene]-3-(prop-2-en-1-yl)-1,3-thiazolidin-4-one	22% inhibiton at 0.01 mM	Fasciola hepatica
(6,7-difluoro-3-methyl-1,4-dioxidoquinoxalin-2-yl)(phenyl)methanone	17% inhibiton at 0.01 mM	Fasciola hepatica
2-methylquinoxaline 1,4-dioxide	8% inhibiton at 0.01 mM	Fasciola hepatica
3-amino-7-([ethyl[(2Z)-3-phenylprop-2-en-1-yl]amino]methyl)quinoxaline-2-carbonitrile 1,4-dioxide	45% inhibiton at 0.01 mM	Fasciola hepatica
3-methyl-N-phenyl-7-([4-[(2E)-3-phenylprop-2-en-1-yl]piperazin-1-yl]methyl)quinoxaline-2-carboxamide 1,4-dioxide	49% inhibiton at 0.01 mM	Fasciola hepatica
3-methyl-N-phenylquinoxaline-2-carboxamide 1,4-dioxide	40% inhibiton at 0.01 mM	Fasciola hepatica
6,7-dichloro-2-methyl-3-(phenylsulfanyl)quinoxaline 1,4-dioxide	22% inhibiton at 0.01 mM	Fasciola hepatica
6-[(E)-[(2Z)-[4-(4-chlorophenyl)-3-(prop-2-en-1-yl)-1,3-thiazol-2(3H)-ylidene]hydrazinylidene]methyl]-2,3-dimethylquinoxaline 1,4-dioxide	2% inhibiton at 0.01 mM	Fasciola hepatica
6-[(E)-[(2Z)-[4-oxo-3-(prop-2-en-1-yl)-1,3-thiazolidin-2-ylidene]hydrazinylidene]methyl]-N,3-diphenylquinoxaline-2-carboxamide 1,4-dioxide	81% inhibiton at 0.01 mM	Fasciola hepatica
7-[ethyl[(2E)-3-phenylprop-2-en-1-yl]amino]-3-methyl-N-phenylquinoxaline-2-carboxamide 1,4-dioxide	54% inhibiton at 0.01 mM	Fasciola hepatica
ethyl 3-methyl-7-[(E)-[2-(prop-2-en-1-ylcarbamothioyl)hydrazinylidene]methyl]quinoxaline-2-carboxylate 1,4-dioxide	58% inhibiton at 0.01 mM	Fasciola hepatica
ethyl 3-methylquinoxaline-2-carboxylate 1,4-dioxide	5% inhibiton at 0.01 mM	Fasciola hepatica
ethyl 3-phenyl-7-([4-[(2E)-3-phenylprop-2-en-1-yl]piperazin-1-yl]methyl)quinoxaline-2-carboxylate 1,4-dioxide	61% inhibiton at 0.01 mM	Fasciola hepatica
ethyl 3-phenyl-7-[(E)-[2-(prop-2-en-1-ylcarbamothioyl)hydrazinylidene]methyl]quinoxaline-2-carboxylate 1,4-dioxide	86% inhibiton at 0.01 mM	Fasciola hepatica
ethyl 6,7-dichloro-3-phenylquinoxaline-2-carboxylate 1,4-dioxide	35% inhibiton at 0.01 mM	Fasciola hepatica
methyl (2E)-2-[(2,3-dimethyl-1,4-dioxidoquinoxalin-6-yl)methylidene]hydrazinecarboxylate	3% inhibiton at 0.01 mM	Fasciola hepatica
methyl (2E)-2-[(2-amino-3-cyano-1,4-dioxidoquinoxalin-6-yl)methylidene]hydrazinecarboxylate	27% inhibiton at 0.01 mM	Fasciola hepatica
additional information	cathepsin L inhibitors with activity against the liver fluke identified from a focus library of quinoxaline 1,4-di-N-oxide derivatives, library screening, overview. Analysis of me-ligand interactions in silico by molecular docking and molecular dynamic (MD) simulations. The compounds readily kill newly excysted juveniles of Fasciola hepaticaa in vitro and have low cytotoxicityin a Hep-G2 cell line and bovine spermatozoa. No inhibition by quinoxaline-2-carbaldehyde 1,4-dioxide, 3-aminoquinoxaline-2-carbonitrile 1,4-dioxide, 3-amino-6,7-dichloroquinoxaline-2-carbonitrile 1,4-dioxide, and 3-methyl-N-phenyl-7-[(E)-[2-(prop-2-en-1-ylcarbamothioyl)hydrazinylidene]methyl]quinoxaline-2-carboxamide 1,4-dioxide	Fasciola hepatica
N,3-diphenyl-6-[(E)-[2-(prop-2-en-1-ylcarbamothioyl)hydrazinylidene]methyl]quinoxaline-2-carboxamide 1,4-dioxide	79% inhibiton at 0.01 mM	Fasciola hepatica
[1,4-dioxido-3-(trifluoromethyl)quinoxalin-2-yl](phenyl)methanone	22% inhibiton at 0.01 mM	Fasciola hepatica
[6,7-difluoro-1,4-dioxido-3-(trifluoromethyl)quinoxalin-2-yl](phenyl)methanone	38% inhibiton at 0.01 mM	Fasciola hepatica

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
extracellular	the enzyme is secreted	Fasciola hepatica	-	-

Organism

Organism	UniProt	Comment	Textmining
Fasciola hepatica	B3TM67	-	-

Synonyms

Synonyms	Comment	Organism
FhCL3	-	Fasciola hepatica

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Fasciola hepatica