| Autor: |
Manfredini S; Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy., Marastoni-M, Tomatis R, Durini E, Spisani S, Pani A, Marceddu T, Musiu C, Marongiu ME, La Colla P |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2000 Mar; Vol. 8 (3), pp. 539-47. |
| DOI: |
10.1016/s0968-0896(99)00317-x |
| Abstrakt: |
Due to the capability of peptidyl derivatives of araC to behave as prodrugs of this antimetabolite, and because of the well known biological properties of peptide T and its analogues (in particular that of targeting CD4+ cells), new peptide T-araC conjugates were prepared and tested in vitro for antiproliferative activity. The aim was that of specifically delivering the antitumor drug to CD4+ cells. N4-(Acylpeptidyl)-derivatives of araC were synthesized by a new general approach involving solid-phase synthesis, which allows mild conditions, avoids the usually required protection of the glycoside portion of nucleosides and affords high yields of the final products. After the demonstration that peptide T-araC conjugates were able to activate chemotaxis by binding CD4 receptor on monocyte membranes, the antiproliferative activity was evaluated against a panel of leukemia lymphoma and carcinoma cell lines derived from human tumors, three CD4+ cell lines included. Title compounds resulted effective as antiproliferative agents at concentrations 4- to 10-fold higher than those of araC alone, did not preferentially inhibit CD4+ cells and proved stable not only in cell culture medium containing 20% FCS, but also in human plasma. All this suggests their potential utility in vivo. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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Full Text from ScienceDirect