TARGETING STAT3 IN CANCER INHIBITION

Palma, G.; D’Aiuto, M.; Petrillo, A.; Dallemagne, P.; Sinicropi, M. S.; Rodriquez, M.; Longo, P.; Mariconda, A. L.; Arra, C.; De Martino, F.; Capasso, A.; Saturnino, Carmela; Mariconda, Annaluisa

Signaltransducerandactivatoroftranscription3(STAT3)regulatesmanycriticalfunctionsinhumannormalandmalignanttissues,suchasdifferentiation,proliferation,survival,angiogenesisandimmunefunction.ConstitutiveactivationofSTAT3isimplicatedinawiderangeofhumancancers.Assuch,STAT3hasbeenstudiedasatumortherapeutictarget.ThelastapproachusingsmallmoleculeSTAT3inhibitorshasbeenthemostexaminedsoHeterocylesandCarbazole.Heterocylesareanessentialclassofmolecules,assumingaroleinmanyaspectofourlife.Indeedheterocyclicnucleusisacommonfeatureofseveralbiomoleculeandbioactivecompoundsincludingagrochemicalproductsanddrugs.Inthisreviewwefocusedontwoimportantclassofheterocycliccompounds:carbazolesandNHCs(N-heterocycliccarbenes)andthereimplicationsincancerinhibitions.Carbazoles,prevalentasstructuralmotifsinvarioussyntheticmaterialsandnaturallyoccurringalkaloids,asisknown,havemanyapplicationsespeciallyaspromisingbioactivecompoundsduetotheirbiologicalproperties,knownsince1965.FurthermoreNHCsareaclassofstablecarbenesthatoverthelastfewyearshaveenteredthefieldas“new”ligandsforbioactivecoordinationcompounds.IthasbeendemonstratedthatmetalNHCcomplexescanbeusedtodevelophighlyefficientmetalbaseddrugswithpossibleapplicationsinthetreatmentofcancerorinfectiousdiseases.