Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
THE SYNTHESIS AND BIOLOGICAL ACTIVITY OF NOVEL ALKYLGLYCEROL DERIVATIVES AS INHIBITORS OF PROTEIN KINASE C ACTIVITY, NEOPLASTIC CELL GROWTH, AND HIV-1 INFECTIVITY
Diss Abstr Int [B]; 52(1):255 1991. Unique Identifier : AIDSLINE ICDB/92677125 Marasco CJ; Univ. of North Carolina at Chapel Hill
Abstract:
The goal of this research was to develop more potent alkyl lipid inhibitors of protein kinase C (PKC), and thus, to potentially augment the antineoplastic and anti-HIV-1 effect of these derivatives. Although several analogs were shown to be more potent or at least equipotent inhibitors of PKC (5B, 19F and 25) than the reference compound 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine, an increase in HL60 cell growth inhibition was not observed. In addition, the quaternary ammonium and alkyl phosphocholine analogs have been shown to inhibit HIV plaque formation using a syncytial plaque assay. These lipids have been shown to inhibit HIV infectivity by shifting the site of viral assembly from the T-cell plasma membrane to intracytoplasmic vacuoles. The most potent analog rac-3-octadecanamido-2-ethoxypropan-1-ol-phosphocholine (AM-18-OEt, not synthesized by the author) exhibited an IC50 for the inhibition of HIV plaque formation of 0.16 uM which was 84-fold lower than the IC50 value determined for CEM-SS cell growth inhibition. Preliminary data has indicated that mixtures of AM-18-OEt and AZT might act synergistically. Based upon these data ether lipids were conjugated to the 5' position of AZT and DDI via phosphate or phosphonate esters, and a carboxylate ester which was contained in a phosphocarnitine functionality. Several of these analogs, 34A and 41, displayed an increased differential selectivity (IC50 for uninfected CEM-SS cell growth/IC50 for inhibition of syncytial plaque formation in HIV-1 infected CEM-SS cells) of 1793 and 3321 respectively, over that of AZT alone (1281). These data indicate that ether lipids, either as a separate entity or conjugated to anti-HIV-1 nucleosides, are both novel and selective agents for suppressing HIV-1 replication and infectivity. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-15649).
Keywords: Antineoplastic Agents/CHEMICAL SYNTHESIS/*PHARMACOLOGY Antiviral Agents/CHEMICAL SYNTHESIS/*PHARMACOLOGY Glycerin/*PHARMACOLOGY Human HIV-1/*DRUG EFFECTS Lipids/*PHARMACOLOGY Protein Kinase C/*ANTAGONISTS & INHIB THESIS
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
