Retinoic acid conjugates as potential antitumor agents: Synthesis and biological activity of conjugates with Ara-A, Ara-C, 3(2H)-furanone, and aniline mustard moieties

MANFREDINI, Stefano; SIMONI, Daniele; FERRONI, Roberto; Rita Bazzanini, †; VERTUANI, Silvia; Sigrid Hatse, †; Jan Balzarini, §; Erik, De Clercq

doi:10.1021/jm9602322

CINECA IRIS Institutional Research Information System

IRIS è la soluzione IT che facilita la raccolta e la gestione dei dati relativi alle attività e ai prodotti della ricerca. Fornisce a ricercatori, amministratori e valutatori gli strumenti per monitorare i risultati della ricerca, aumentarne la visibilità e allocare in modo efficace le risorse disponibili.

In a dual targeting approach, to explore the ability of tretinoin (all- trans-retinoic acid) to behave as a covalent carrier for cytotoxic entities, conjugates of retinoic acid with a few representative molecules, being important examples of antitumor pharmacophores (i.e., nucleoside analogues and alkylating agents), have been synthesized and tested for their cytostatic and differentiating activity. All compounds were stable to in vitro hydrolysis in human plasma and more lipophilic than the parent compounds, thus consenting enhanced uptake into the cells. Among the nucleoside analogues the Ara-C derivatives 3 and 6 and the Ara-A derivative 7 proved the most cytostatic (IC50 < 0.32 μg/mL) resulting from 25- to >144-fold more active (Ara-A derivatives) or at least as equally active (Ara-C derivatives) as compared to the parent nucleosides. Compound 3, endowed with a highly lipophilic silyl moiety at the 3' and 5' positions, showed the highest differentiating activity (54% and 44% differentiated HL-60 cells at 0.2 and 0.05 μg/mL respectively). With regard to the retinoic acid conjugates of alkylating agents, compound 10 was the most cytostatic agent (IC50 < 0.32 μg/mL) and the most potent differentiating agent (33-34% at 0.32 and 0.08 μg/mL). These structures may also be regarded as analogs of either retinoic acid or the cytotoxic compound.

Scheda prodotto non validato

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Titolo:	Retinoic acid conjugates as potential antitumor agents: Synthesis and biological activity of conjugates with Ara-A, Ara-C, 3(2H)-furanone, and aniline mustard moieties
Autori:	MANFREDINI, Stefano SIMONI, Daniele FERRONI, Roberto Rita Bazzanini, † VERTUANI, Silvia Sigrid Hatse, † Jan Balzarini, § Erik, De Clercq mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	1997
Rivista:	JOURNAL OF MEDICINAL CHEMISTRY
Handle:	http://hdl.handle.net/11392/2355922
Appare nelle tipologie:	03.1 Articolo su rivista

File in questo prodotto:

Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.