Antitumor activity of SRI 62‐834, a cyclic ether analog of ET‐18‐OCH₃

Abstract

SRI 62-834, an analog of the antitumor agent ET-18-OCH3 in which the oxygen atom at carbon atom 2 has been incorporated into a five-membered heterocycle, has been prepared and evaluated as an antitumor agent. The compound exhibited good cytotoxicity in vitro against a variety of tumor cell lines and was as effective as ET-18-OCH3 given orally in the mouse Meth A sarcoma model. SRI 62-834 was shown to be an inhibitor of platelet-derived growth factor (PDGF), possibly at the receptor level, and platelet-activating factor (PAF) at the receptor level.

Testing the hypothesis that amphiphilic antineoplastic lipid analogues act through reduction of membrane curvature elastic stress

“…SRI 62.834 (13), which differs substantially from ET-18-OMe through its cyclic headgroup, still retains a type I molecular shape and is also highly cytotoxic (Houlihan et al 1987;Dive et al 1991). Similarly, the O -alkylethyleneglycophosphocholine homologues have type I molecular shape and are also cytotoxic (Honma et al 1983).…”

Synthesis of chiral tetrahydrofuran derivatives

“…THF derivative 3d is a key intermediate for the synthesis of the bioactive compound (S)-SRI-62-834 14 (Scheme 4), an antitumor agent 8 , that has been obtained previously by a multistep sequence that includes enzymatic resolution of the acetylated tetrahydrofuran-2,2-methanol. Spirodilactone 2g was obtained from substituted lactone 2f by simple lactonisation.…”

“…Derivatives of 2,2-disubstituted tetrahydrofurans have elicited attention as antitumor agents 8 and potent VLA-4 antagonists, 9,10 which could be useful in the treatment of various VLA-4 dependent inflammatory diseases such as asthma, multiple sclerosis and arthritis. 1,7-Dioxaspiro [4.4]nonane (spiroditetrahydrofuran) skeleton exists in the naturally occurring prehispanolones, 11 leopersins, 12 syringolides.…”

The Role of Adhesion Receptors in Melanoma Metastasis and Therapeutic Intervention Thereof

“…One difference is that exposition with edelfosine leads to selective promotion of apoptosis in leukemic cells (Mollinedo et al, 1997;Gajate et al, 2000;. Edelfosine was tested as a pharmaceutical compound against prostate cancer (Berdel et al, 1981), human brain tumors, lung tumors and other cancer types (Berdel et al 1984;Denizot et al, 2001;Haugland et al, 1999;Houlihan et al, 1987;Kosano & Takatani, 1988;Ausili et al, 2008). In detail, edelfosine exposition leads to accumulation in lipid rafts (van der Luit et al, 2002; and to a reorganization of the lipid and protein composition of membrane caveolae Zaremberg et al, 2005;Gajate & Mollinedo, 2007).…”