Pure Appl. Chem., 2001, Vol. 73, No. 9, pp. 1437-1444
doi:10.1351/pac200173091437
Retinoic acid and analogs as potent inducers of differentiation and apoptosis. New promising chemopreventive and chemotherapeutic agents in oncology*
Daniele Simoni,#, Riccardo Rondanin, Riccardo Baruchello, Marinella Roberti, Marcello Rossi, Stefania Grimaudo, Natale D'Alessandro, Francesco Paolo Invidiata, and Manlio Tolomeo
1Dipartimento di Scienze Farmaceutiche, Via Fossato di Mortara 17-19, Università di Ferrara, 44100 Ferrara, Italy; 2Dipartimento di Scienze Farmaceutiche, Università di Bologna, Italy; 3Divisione di Ematologia e Servizio AIDS, Policlinico di Palermo, Italy; 4Dipartimento di Scienze Farmacologiche, Università di Palermo, Italy; 5Dipartimento Farmacochimico Tossicologico e Biologico, Università di Palermo, Italy
Abstract:
In this report we will describe the preparation and the biological activity of a novel class of heterocyclic arotinoids endowed with potent cytotoxic and apoptotic acitivity. Structureactivity relationship studies revealed that the different stereochemistry at the C9 double bond of retinoids seems associated with a different biological activity: potent apoptotic activity for the cis-isomers, whereas differentiating activity for the trans structures. An interesting modified Wittig procedure that allows easily to arotinoids will also be described. The substitution of the alkenyl portion with a more flexible oxymethyl or aminomethyl moiety gave compounds with poor activity, whereas isoxazole-bridged arotinoids allowed compounds active also on multidrug-resistant (MDR) leukemia cell lines.