Correlation of Anti-HIV Potency with Lipophilicity in a Series of Cosalane Analogs Having Normal Alkenyl and Phosphodiester Chains as Cholestane Replacements

Abstract

In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl substituents were found to be more potent as inhibitors of the cytopathic effect of HIV-1 in cell culture than the phosphodiesters. In addition, the potencies of the alkene congeners correlated positively with chain length and lipophilicity of the alkene. The results indicate that the cholestane moiety of cosalane functions as a lipophilic accessory appendage to escort the dichlorodisalicylmethane pharmacophore to a lipid environment.

A magnetic iron(iii) switch with controlled and adjustable thermal response for solution processing

“…The syntheses of 1-bromotriacontane, 25 complexes 1a-e, 17,18 and 2c-e 17 were reported previously, all other reagents were used as received. For synthesis, THF was dried by passage through a solvent purification column, all other reagents were commercially available and used as received.…”

Transport of Cosalane—A Highly Lipophilic Novel Anti‐HIV Agent—Across Caco‐2 Cell Monolayers

“…Cosalane (NSC 658586; Figure 1) is a potent inhibitor of HIV replication with a broad range of activity against a variety of HIV‐1 isolates, HIV‐2, Rauscher murine leukemia virus, HSV‐1, HSV‐2, and human cytomegalovirus 1–5. It acts primarily by inhibiting the binding of gp120 to CD4, as well as by inhibiting a post‐attachment event prior to reverse transcriptase action 1.…”

Synthesis and anti-HIV activity of a bile acid analog of cosalane

“…Previous studies have demonstrated a correlation of anti-HIV potency with lipophilicity in a series of cosalane analogs having normal alkenyl and phosphodiester chains as cholestane replacements. 24 Moreover, recent evidence indicates that cosalane may in fact accumulate in the lipid bilayer of the hepatocyte membranes. 25 The decrease in lipophilicity of the steroid fragment of the bile acid analog 9 versus cosalane 1 may therefore be at least partially responsible for the observed decrease in antiviral potency.…”