Anti-AIDS (Acquired Immune Deficiency Syndrome) Agents. 17. New Brominated Hexahydroxybiphenyl Derivatives as Potent Anti-HIV Agents

Abstract

Sixteen biphenyl derivatives were synthesized and evaluated for their inhibitory activity against HIV-1 replication in acutely infected H9 cells. 3-Bromo- (4) and 3,3'-dibromo-4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-2,2'- bis(methoxycarbonyl)biphenyl (5) demonstrated potent anti-HIV activity with EC50 values of 0.52 and 0.23 micrograms/mL and therapeutic index values of > 190 and > 480, respectively. A comparison of the anti-HIV activity of these biphenyl derivatives suggested that the types of substituents on the phenolic hydroxy groups rather than the number of bromine(s) on the aromatic rings are important to the enhanced anti-HIV activity. Compounds 4 and 5 also showed potent inhibitory activity against HIV-1 reverse transcriptase in a template-primer dependent manner. The site of inhibition of HIV could be related to inhibition of this enzyme. Compounds 4 and 5 did not induce virus expression from the chronic HIV-1-infected cell lines ACH-2 and U1. Furthermore, these two agents did not inhibit an increase in virus production from the chronic HIV-1-infected cell lines when the phorbol ester PMA was present.

Cancer preventive agents 11. Novel analogs of dimethyl dicarboxylate biphenyl as potent cancer chemopreventive agents†

“…Chemistry DDB analogs (Table 1) were synthesized following literature methods (Xie et al, 1995). Reduction of 1 and 3,3′-dibromo-DDB (2) with diisobutylaluminum hydride (DIBAL) resulted in the related 2,2′-methylene alcohols 21 and 3, respectively (Figure 2).…”

“…In our design of new DDB analogs, we found that known DDB analogs with different functional groups were previously synthesized and tested for cancer preventive ability (Xie et al, 1995). In addition, while many 2,2′-carboxylate ester derivatives have been covered in various patents and papers, the modification of a 2,2′-bismethylene alcohol DDB intermediate (21) appears to be a new avenue of exploration.…”

Hydrolyzable Tannins (Chebulagic Acid and Punicalagin) Target Viral Glycoprotein-Glycosaminoglycan Interactions To Inhibit Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread

“…The anti-herpes activities of hydrolyzable tannins are thought to be dependent on the number of galloyl or HHDP groups, irrespective of the sugar core (71). Structures containing HHDP unit have also been valuable pharmacophores for inhibiting HIV enzymatic activities (20,75). Indeed, anti-HIV activities from CHLA, CHLI, PUG, and PUN have been reported to prevent binding of recombinant HIV gp120 to CD4 and to exert inhibitory effects on HIV-1 RT and integrase (1,51,74).…”

Absolute configurations and CD spectra of axially chiral biphenyls prepared in a facile manner by crystallization‐induced configuration transformation

“…[37][38][39][40] The schisantherin D-related biphenyl, dimethyl-4,4 0 -dimethoxy-5,6,5 0 ,6 0 -bis(methylenedioxy)-biphenyl-2,2 0 -dicarboxylate (DDB, 2), 41 shows antiviral activity and has been used to treat HBV infection. 42 The four ortho-substituents of DDB inhibit rotation about the biphenyl axis, and the two isomers show different biological activities.…”