Cosalane Analogs with Enhanced Potencies as Inhibitors of HIV-1 Protease and Integrase

Abstract

Several new analogues of the novel anti-HIV agent cosalane have been synthesized and evaluated as inhibitors of HIV-1 integrase and protease, HIV-1 replication, HIV-1 and HIV-2 cytopathicity, HIV-1- and HIV-2-mediated syncytium formation, and cytopathicity of a variety of human pathogenic viruses. The congeners displayed enhanced potencies relative to cosalane itself as inhibitors of HIV-1 integrase and protease. The two most potent analogues against HIV-1 integrase displayed IC50 values of 2.2 microM, while the three most potent compounds against HIV-1 protease had IC50 values in the 0.35-0.39 microM range. In addition to its activity against HIV-1 and HIV-2 cytopathicity, cosalane inhibited the cytopathic effects of herpes simplex virus-1, herpes simplex virus-2, and human cytomegalovirus at concentrations that were well below the cytotoxic concentrations. Potentially useful antiviral activities were also revealed for some of the new cosalane congeners against influenza virus, Junin virus, and Tacaribe virus.

Anti‐human immunodeficiency virus activity of 3,4,5‐tricaffeoylquinic acid in cultured cells of lettuce leaves

“…Disintegration activity of aurintricarboxylic acid [8], cosalene analogs [9], flavones, caffeic acid phenethyl ester [10], and other compounds [11] was reported to be effective. However, some of them interfered with retro-virus transcriptase and showed low selectivity in the active sites or could not detect any increase of vital cells against HIV infection.…”

Structural features and anti-HIV-1 activity of novel polysaccharides from red algae Grateloupia longifolia and Grateloupia filicina

“…Studies with DS resistant mutants of HIV show that the interaction of DS with its target is specific. DS resistance is associated with specific gp120 mutations, some of which are associated with, and give cross resistance to other classes of entry inhibitors including the bicyclams, synthetic peptide antagonists of the CXCR4 coreceptor, and aurintricarboxylic acid (ATA) which inhibits via the V3 loop and CD4 binding site [4,7,10,11].…”

HIV-1 Integrase Inhibitors: A Review of Their Chemical Development

“…A substituted catechol moiety is common in HIV-1 IN inhibitors, such as bis-catechols [27][28][29], caffeic acid phenethyl ester (CAPE; Figure 5) [30], flavones and flavonoids [31][32][33][34][35][36][37][38].…”