6533b7dbfe1ef96bd1270273
RESEARCH PRODUCT
Synthesis and Biological Evaluation of 2-Amino-3-(3’,4’,5’-Trimethoxybenzoyl)-6-Substituted-4,5,6,7-Tetrahydrothieno[2,3-c]pyridine Derivatives as Antimitotic Agents and Inhibitors of Tubulin Polymerization
Antonietta Di CristinaMaria Rosaria PipitonePier Giovanni BaraldiErnest HamelTaradas SarkarStefania GrimaudoAndrea BrancaleOlga Cruz-lopezJan BalzariniCarlota Lopez CaraManlio TolomeoMaria Dora CarrionRomeo RomagnoliSahar Kandilsubject
PyridinesStereochemistryClinical BiochemistryPharmaceutical ScienceAntimitotic AgentsCrystallography X-RayBiochemistryChemical synthesisArticleInhibitory Concentration 50Structure-Activity Relationshipchemistry.chemical_compoundTubulinMicrotubuleDrug DiscoveryPyridineAnimalsStructure–activity relationshipCytotoxicityMolecular BiologyMolecular StructurebiologyBicyclic moleculeChemistryOrganic ChemistryTubulinbiology.proteinMolecular MedicineAntimitotic Agentdescription
Microtubules are among the most successful targets of compounds potentially useful for cancer therapy. A new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-4,5,6,7-tetrahydrothieno[b]pyridine molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-amino-3-(3,4,5-trimethoxybenzoyl)-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[b]pyridine, which inhibits cancer cell growth with IC(50)-values ranging from 25 to 90 nM against a panel of four cancer cell lines, and interacts strongly with tubulin by binding to the colchicine site. In this series of N(6)-carbamate derivatives, any further increase in the length and in the size of the alkyl chain resulted in reduced activity.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-01-01 |