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Novel 3‐benzoyl‐2‐piperazinylquinoxaline derivatives as potential antitumor agents
Author(s) -
Piras Sandra,
Loriga Mario,
Carta Antonio,
Paglietti Giuseppe,
Paola Costi M.,
Ferrari Stefania
Publication year - 2006
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570430304
Subject(s) - chemistry , thymidylate synthase , dihydrofolate reductase , enzyme , stereochemistry , cell culture , inhibitory postsynaptic potential , biochemistry , combinatorial chemistry , cancer , medicine , fluorouracil , biology , genetics , neuroscience
A series of new benzoylquinoxaline derivatives ( 7‐26 ) was synthesized and evaluated for antitumor activity against a panel of 60 human cell lines at the NCI of Bethesda. Among the compounds which have passed the preliminary screening, compound 23 exhibited the best profile and growth inhibition activity at 100 ‐ 10 μM. The compounds were then tested towards a folate‐dependent enzymes bio‐library including Thymidylate synthases enzymes and human Dihydrofolate reductase at 10 μM. The most of compounds exhibited a moderate inhibitory activity towards all or some of the enzymes tested with detectable inhibition constants (K i ) values in the range of 0.6‐70 μM. Compounds 21, 23, 24 showed K i in the range of 10‐38 μM against both hDHFR and hTS.