Retinoic acid and analogs as potent inducers of differentiation
and apoptosis. New promising chemopreventive and chemotherapeutic agents
in oncology*
Daniele Simoni1,#, Riccardo Rondanin1, Riccardo Baruchello1, Marinella
Roberti2, Marcello Rossi1, Stefania Grimaudo3, Natale D'Alessandro4,
Francesco Paolo Invidiata5, and Manlio Tolomeo3
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.
*Plenary lecture presented at the Hungarian-German-Italian-Polish
Joint Meeting on Medicinal Chemistry, Budapest, Hungary, 2 6 September
2001. Other presentations are published in this issue, pp.
1387-1509.
# Corresponding author.
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