Depsides and Depsidones as Inhibitors of HIV-1 Integrase:  Discovery of Novel Inhibitors through 3D Database Searching

Abstract

Seventeen lichen acids comprising despides, depsidones, and their synthetic derivatives have been examined for their inhibitory activity against HIV-1 integrase, and two pharmacophores associated with inhibition of this enzyme have been identified. A search of the NCI 3D database of approximately 200,000 structures yielded some 800 compounds which contain one or the other pharmacophore. Forty-two of these compounds were assayed for HIV-1 integrase inhibition, and of these, 27 had inhibitory IC50 values of less than 100 microM; 15 were below 50 microM. Several of these compounds were also examined for their activity against HIV-2 integrase and mammalian topoisomerase I.

The investigation of cytogenetic and oxidative effects of diffractaic acid on human lymphocyte cultures

“…Many of the lichen acids have biological effects due to antioxidant properties. However, only a few reports concerning the antioxidative nature of pure lichen metabolites are available (Neamati et al 1997;Silva et al 2010). For assessing the antioxidant/oxidant effects of DA, total antioxidant capacity (TAC) and total oxidant status (TOS) assays were performed.…”

“…It is commonly isolated from the lichens such as Usnea longissima, U. diffracta, Parmelia tinctorum and P. nepalensis (Bayır et al 2006). Studies have shown that DA has analgesic, antiviral and antitumoral activities (Okuyama et al 1995;Yamamota et al 1995;Neamati et al 1997). However, the information regarding the cytotoxic, cytogenetic and oxidative effects of DA in human blood cells remain unknown.…”

Bioproduction of Depsidones for Pharmaceutical Purposes

“…These two steps, called processing 3 'and band transfer of DNA can be measured in vitro using a purified recombinant integrase and a 21-mer duplex oligonucleotide corresponding to the end-HIV U5 LTR sequence (Vlietinck et al, 1998). Using a 3D database of the National Institute of Cancer and the appropiate software (Chem-X), Neamati et al (1997) have identified two potential architectures of active pharmacophores for virensic acid and other depsidones such as physodic acid. Both compounds, as well as granulatine (the methylester of virensic acid), exhibit high potential for inhibition of viral integrase processing activity for both 3' processing and for the transfer belt.…”

Anti-Respiratory Syncytial Virus Agents from Phytomedicine

“…Some lichens and lichen-derived substances have been shown to possess anti-viral activities (Cohen et al, 1996;Pengsuparp et al, 1995;Neamati et al, 1997). Ramalina farinacea, a lichen found to Nigeria but also available in other isolated places, has earlier been shown to possess broad anti-retro-viral (including lentiviruses) and anti-adenoviral principles (Esimone et al, 2005).…”