Synthesis of novel derivatives of murrayafoline A and their inhibitory effect on LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells

Cu(I)-catalyzed Huisgen–Meldal–Sharpless type dipolar ‘click’ reactions between azido-tetrathiafulvalene derivatives and ethynylferrocene yield the first examples of ferrocenyl-1,2,3-triazolyl-tetrathiafulvalene assemblies (4a, 4b). The electrochemical behavior of 4a and 4b, which integrate two distinctive redox probes, has been investigated, and their binding ability for various transition-metal cations has been studied by cyclic voltammetry. The contribution of the triazolyl ring in the guest binding process is illustrated by the specific electrochemical recognition of Zn2+ by receptor 4b

2-Aryl- and 2-amido-benzothiazoles as multifunctional vasodilators on rat artery preparations

The neuroprotective agent riluzole [2-amino-6-(trifluoromethoxy)benzothiazole] has been shown to antagonize neuronal high-voltage activated Ca(2+) currents. In the search for novel scaffolds leading to potential antihypertensive agents, a series of 2-aryl- and 2-amido-benzothiazoles (HUP) were assessed for their vasorelaxing property on rat aorta rings and for their L-type Ba(2+) currents [I(Ba(L))] blocking activity on single myocytes isolated from the rat tail artery. HUP5 and HUP30, the most potent of the series, inhibited phenylephrine-induced contraction with IC₅₀ values in the range 3-6 µM. The presence of endothelium did not modify their spasmolytic activity. Both HUP5 and HUP30 increased tissue levels of cGMP and shifted to the left the concentration-response curve to sodium nitroprusside. In rings precontracted by phenylephrine, tetraethylammonium or 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) shifted to the right the concentration-relaxation curves of HUP5 and HUP30. The antispasmodic effect of HUP5 and HUP30 was more marked on rings stimulated with 25/30 mM than with 60 mM K(+). HUP5 and HUP30 antagonized both extracellular Ca(2+) influx and Ca(2+) mobilization from intracellular stores in response to phenylephrine: this effect was not modified by the presence of ODQ. I(Ba(L)) was partly inhibited by HUP5 and blocked by HUP30 in a concentration-dependent as well as ODQ-independent manner. In conclusion, HUP5 and HUP30 are vasorelaxing agents that stimulate soluble guanylyl cyclase, activate K(+) channels, and block extracellular Ca(2+) influx. The present benzothiazole derivatives form a novel class of multifunctional vasodilators which may give rise to effective antihypertensive agents

Litsea Species as Potential Antiviral Plant Sources

Litsea verticillata Hance (Lauraceae), a Chinese medicine used to treat swelling caused by injury or by snake bites, was the first plant identified by our National Institutes of Health (NIH)-funded International Cooperative Biodiversity Group (ICBG) project to exhibit anti-HIV activities. From this plant, we discovered a class of 8 novel litseane compounds, prototypic sesquite rpenes, all of which demonstrated anti-HIV activities. In subsequent studies, 26 additional compounds of different structural types were identified. During our continuing investigation of this plant species, we identified two new litseanes, litseaverticillols L and M, and a new sesquiterpene butenolide, litseasesquibutenolide. Litseaverticillols L and M were found to inhibit HIV-1 replication, with an IC50 value of 49.6μM. To further determine the antiviral properties of this plant, several relatively abundant isolates, including a litseane compound, two eudesmane sesquiterpenes and three lignans, were evaluated against an additional 21 viral targets. Lignans 8 and 9 were shown to be active against the Epstein-Barr Virus (EBV), with EC50 values of 22.0μM (SI=3.8) and 16.2μM (SI>6.2), respectively. Since many antiviral compounds have been discovered in L. verticillata, we further prepared 38 plant extracts made from the different plant parts of 9 additional Litsea species. These extracts were evaluated for their anti-HIV and cytotoxic activities, and four of the extracts, which ranged across three different species, displayed 97-100% inhibitory effects against HIV replication without showing cytotoxicity to a panel of human cell lines at a concentration of 20μg/mL