6533b858fe1ef96bd12b658a
RESEARCH PRODUCT
Beyond Pseudo‐natural Products: Sequential Ugi/Pictet‐Spengler Reactions Leading to Steroidal Pyrazinoisoquinolines That Trigger Caspase‐Independent Death in HepG2 Cells
Gabriela Myriam CabreraSofía L. AcebedoAndrea A. BarqueroAgustín GalileaMarcelo OteroFernando AlonsoPau Arroyo MañezPau Arroyo MañezJavier A. Ramírezsubject
StereochemistryAntineoplastic AgentsSequence (biology)01 natural sciencesBiochemistryPiperazineschemistry.chemical_compoundDrug DiscoveryHumansGeneral Pharmacology Toxicology and PharmaceuticsCell ProliferationPharmacologyBiological ProductsNatural productPictet–Spengler reactionCell DeathMolecular Structure010405 organic chemistryOrganic ChemistryCaspase independentStereoisomerismHep G2 CellsIsoquinolinesChemical space0104 chemical sciences010404 medicinal & biomolecular chemistrychemistryCaspasesIntramolecular forceHepg2 cellsMolecular MedicineUgi reactionSteroidsDrug Screening Assays Antitumordescription
In this work, we describe how stereochemically complex polycyclic compounds can be generated by applying a synthetic sequence comprising an intramolecular Ugi reaction followed by a Pictet-Spengler cyclization on steroid-derived scaffolds. The resulting compounds, which combine a fragment derived from a natural product and a scaffold not found in nature. are both structurally distinct and globally similar to natural products at the same time, and interrogate an alternative region of the chemical space. One of the new compounds showed significant antiproliferative activity on HepG2 cells through a caspase-independent cell-death mechanism, an appealing feature when new antitumor compounds are searched.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-03-31 | ChemMedChem |