6533b860fe1ef96bd12c30c3
RESEARCH PRODUCT
Synthesis of a new class of pyrrolo[3,4-h]quinazolines with antimitotic activity
Anna CarboneGirolamo CirrincioneSilvia TisiIgnazio CastagliuoloOlaf-georg IssingerPatrizia DianaPaola BarrajaDaniela VedaldiVirginia SpanòAlessandra MontalbanoPaola BrunIrina PrimacBarbara ParrinoAlessia Salvadorsubject
Programmed cell deathMitosisAntiproliferative activityCell Line TumorDrug DiscoveryHuman Umbilical Vein Endothelial CellsPiHumansTubulin polymerizationPyrrolesPyrrolo[3Cell-mediated cytotoxicityPyrrolo[34-h]quinazolines Antiproliferative activity Antimitotic activity Tubulin polymerization Vascular disrupting activityTubulin polymerizationVascular disrupting activityPharmacologyMatrigelCell Death4-h]quinazolinesChemistryAntimitotic activityOrganic ChemistryGeneral MedicineSettore CHIM/08 - Chimica FarmaceuticaMitochondriaEndothelial stem cellBiochemistryCell cultureApoptosisPyrrolo[3; 4-h]quinazolines; Antiproliferative activity; Antimitotic activity; Tubulin polymerization; Vascular disrupting activityQuinazolinesLysosomesdescription
Abstract A new series of pyrrolo[3,4- h ]quinazolines was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular cytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI 50 values reaching the low micromolar level (1.3–19.8 μM). These compounds were able to induce cell death mainly by apoptosis through a mitochondrial dependent pathway. Selected compounds showed antimitotic activity and a reduction of tubulin polymerization in a concentration-dependent manner. Moreover, they showed anti-angiogenic properties since reduced in vitro endothelial cell migration and disrupted HUVEC capillary-like tube network in Matrigel.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 |