HIV inhibitory activity

In 2000, Boyd et al. described the isolation of siamenol (89) from the organic extract of M. siamensis (85). Siamenol exhibited HIV-inhibitory activity. The UV... 

Clauszoline-K and dausine C (clauszoline-L) have been isolated from the stem bark of the Chinese medidnal plant Clausena excavata [72], Clausine M and dausine N have been found in the root bark of the same plant [73]. The bioassay-guided fractionation of the organic extract of Murraya siamensis, collected in Thailand, led to the isolation of siamenol, which shows HIV-inhibitory activity [74], A simple route to these 7-oxygenated carbazole alkaloids has been developed, based on a highly efficient palladium-catalyzed approach (Scheme 15.21) [75] (Table 15.4). 

Bioassay-guided fractionation of an aqueous extract from a Philippine Islands collection of the soft coral Lohophytum spp. yielded cembranoid diterpenes, Fig. (3), which exhibited moderate HIV-inhibitory activity in a cell-based in vitro anti-HIV assay [44], while new isomalabaricane triterpenes. Fig. (4), have been isolated from the sponge Stelletta spp. [45]. Other anti-HIV diterpenes also included the dolabellane diterpenes isolated from the Brazilian brown algae Dictyota pfaffi [46] and Dictyota menstrualis [47]. To investigate the effect of these diterpenes in the reverse transcription of the viral genomic RNA, the recombinant HIV-1 RT was assayed in vitro in the presence of each compound. All compounds inhibited the RNA-dependent DNA-polymerase activity of HIV-1 RT and consequently virus replication. 

Prabhakar, Y.S., Rawal, R.K., Gupta, S., Solomon, V.R. and Katti, S.B. (2005) Topological descriptors in modeling the HIV inhibitory activity of 2-aryl-3-pyridyl-thiazolidin-4-ones. Comb. Chem. High T. Scr., 8, 431-437. 

Cyclic peptide antibiotic. Constit. of Chassalia parvifolia. Shows HIV-inhibitory activity. Incorrectly indexed in CA. 

Resveratrol (3,5,4 -trihydroxystilbene) is a natural component of certain foods, such as grapes, has been shown to have anti-HSV activities in vitro and in vivo (Fig. 3.6 Docherty et al. 2004, 2005). Moreover, resveratrol was found to inhibit varicella-zoster virus (VZV) replication in a dose-dependent and reversible manner (Docherty et al. 2006). Two oligostilbenes dibalanocarpol and balanocarpol isolated from the leaves of Hopea malibato exhibited very modest HIV-inhibitory activity in vitro (Dai et al. 1998). 

We have recently reported the potent in vitro HIV inhibitory activity of 4 -azido-thymidine. This compound is unique among all other nucleoside inhibitors because it retains the 3 -hydroxyl group. However, in spite of the presence of a 3 -hydroxyl group, it too can act as a chain terminator besides being a potent reverse transcriptase inhibitor. In order to delineate the breadth of activity as it extends over other 4 -substituted nucleosides, we have synthesized a series of analogues. In this series, we have varied the base while an azido group remained at the 4 -position, we have made substitutions at the 3 -position of 4 -azidothymidine, and we have examined the effect of other substituents at the 4 -position of thymidine. From these studies some general trends in structure—activity relationships are evident. 

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