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Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of

Justicia gendarussa, a medicinal plant collected in Vietnam, was identified as a potent anti-HIV-1 active lead from the evaluation of over 4500 plant extracts. Bioassay-guided separation of the extracts of the stems and roots of this plant led to the isolation of an anti-HIV arylnaphthalene lignan (ANL) glycoside, patentiflorin A (1). Evaluation of the compound against both the M- and T-tropic HIV-1 isolates showed it to possess a significantly higher inhibition effect than the clinically used anti-HIV drug AZT. Patentiflorin A and two congeners were synthesized, de novo, as an efficient strategy for resupply as well as for further structural modification of the anti-HIV ANL glycosides in the search for drug leads. Subsequently, it was determined that the presence of a quinovopyranosyloxy group in the structure is likely essential to retain the high degree of anti-HIV activity of this type of compounds. Patentiflorin A was further investigated against the HIV-1 gene expression of the R/U5 and U5/gag transcripts, and the data showed that the compound acts as a potential inhibitor of HIV-1 reverse transcription. Importantly, the compound displayed potent inhibitory activity against drug-resistant HIV-1 isolates of both the nucleotide analogue (AZT) and non-nucleotide analogue (nevaripine). Thus, the ANL glycosides have the potential to be developed as novel anti-HIV drugs.

Natural products, explicitly medicinal plants, are an important source of inspiration of antitumor drugs, because they contain astounding amounts of small molecules that possess diversifying chemical entities. For instance, Isodon (formerly Rabdosia), a genus of the Lamiaceae (formerly Labiatae) family, has been reported as a rich source of natural diterpenes. In the current study, we evaluated the in vitro anti-proliferative property of flexicaulin A (FA), an Isodon diterpenoid with an ent-kaurane structure, in human carcinoma cells, by means of cell viability assay, flow cytometric assessment, quantitative polymerase chain reaction array, Western blotting analysis, and staining experiments. Subsequently, we validated the in vivo antitumor efficacy of FA in a xenograft mouse model of colorectal carcinoma. From our experimental results, FA appears to be a potent antitumor molecule, since it significantly attenuated the proliferation of human colorectal carcinoma cells in vitro and restricted the growth of corresponsive xenograft tumors in vivo without causing any adverse effects. Regarding its molecular mechanism, FA considerably elevated the expression level of p21 and induced cell cycle arrest in the human colorectal carcinoma cells. While executing a non-apoptotic mechanism, we believe the antitumor potential of FA opens up new horizons for the therapy of colorectal malignancy.

In a search for new anti-HIV active leads from over several thousands of plant extracts, we have identified a potent plant lead. The active plant is determined as Justicia gendarussa (Acanthaceae), a medicinal plant that has been used for the treatment of injury, arthritis and rheumatism in Asia including China. Our bioassay-guided fractionation of the methanol extract of the stems and barks of the plant led to the isolation of two anti-HIV compounds, justiprocumins A and B. The compounds are identified as new arylnaphthalide lignans (ANL) glycosides. We further determined that the ANL glycosides are the chemical constituents that contribute to the anti-HIV activity of this plant. Justiprocumin B displayed potent activity against a broad spectrum of HIV strains with IC50 values in the range of 15–21 nM (AZT, IC50 77–95 nM). The compound also displayed potent inhibitory activity against the NRTI (nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-11617-1) of the analogue (AZT) as well as the NNRTI (non-nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-1N119) of the analogue (nevaripine).

Ethnopharmacological relevance Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. Aim of the study The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. Materials and methods The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A ( 1 ) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum . They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans , Porphyromonas gingivalis and Candida albicans . Results Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A ( 1 ) and lophanic acid ( 2 ). Fladin A ( 1 ) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid ( 2 ) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8 μg/mL, and fladin A ( 1 ) also showed inhibition activity against the fungus with a MIC value of 62.5 μg/mL. Conclusions Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study.

Neutral salicylaldiminato Ni(II) complexes bearing a single N -heterocyclic carbene (NHC) ligand [3,5- t Bu 2 -2-(O)C 6 H 2 CH NAr]Ni(C{RNCHCHN i Pr})Ph [Ar = 2,6- i Pr 2 C 6 H 3 , R = Bn ( 1 ); Ar = 2,6- i Pr 2 C 6 H 3 , R = i Pr ( 2 )], have been synthesized via a one-pot procedure in high yield. The X-ray structure analysis reveals that both of 1 and 2 adopt distorted square-planar coordination geometry and NHC carbon (C carbene ) is trans to the ketimine nitrogen. Preliminary study indicates that complex 1 is inert toward the insertion of ethylene, however, it can catalyze the dimerization of ethylene in the presence of modified methylaluminoxane (MMAO) with a moderate activity of 3.05 × 10 4 g(mol Ni) −1 h −1 atm −1 in a highly selective fashion.

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).

The reaction of anhydrous FeBr2 with two equivalents of in situ generated anionic aryloxo-functionalized N-heterocyclic carbene [NaO-4,6-di-C(CH3)3-C6H2-2-CH2{C(NCHCHNR)}] (R = CH(CH3)2, NaL1; R = CH2Ph, NaL2) affords two bis-ligand Fe(II) complexes FeL 2 1 (1) and FeL 2 2 (2) in good yield, respectively. Attempt to synthesize mono-ligand Fe(II) bromide by the 1:1 molar ratio of NaL to FeBr2 is unsuccessful, the same complexes of 1 and 2 were obtained. Both of 1 and 2 have been fully characterized by elemental analysis, 1H NMR spectra and X-ray structure determination. Preliminary studies show that 1 can catalyze the ring-opening polymerization of e-caprolactone as a single component catalyst. The mechanism of the present ROP of e-caprolactone has been investigated by the end group analysis.

The catalytic activity of a series of indenylnickel(II) halides: (1-R-Ind)Ni(PPh3)X (R=ethyl, cyclopentyl and benzyl, while X=Cl, Br and I), towards styrene polymerization was studied in the presence of NaBPh4 and PPh3. The catalytic property of these halides was related to the substituent group on the indenyl ligand and the halogen atom bonded to the metal atom. Among them, the (1-Et-Ind)Ni(PPh3)Cl/NaBPh4/PPh3 system showed the highest activity for the polymerization of styrene, and the polystyrene obtained was a syndio-rich (rr triad) atactic polymer with Mn values in the range of 103–104. The mechanism of the styrene polymerization initiated by the (1-Et-Ind)Ni(PPh3)Cl/NaBPh4/PPh3 system was studied.

The reaction of Ni(PPh3)2Br2 with two equivalents of anionic aryloxo-functionalized N-heterocyclic carbene [NaO-4,6-di-tBu-C6H2-2-CH2{C(NCHCHNR)}] (R = iPr, NaL1; R = Bz, NaL2), which are generated in situ by the reaction of the corresponding salt H2LCl with two equivalents of NaN(SiMe3)2, affords bis-ligand complexes of L 2 1 Ni (3) and L 2 2 Ni (4) in good yield, respectively. It is interesting to note that still the bis-ligand one not the mono-ligand Ni(II) halide is obtained, even the molar ratio of NaL1or NaL2 to Ni(PPh3)2Br2 is changed to 1:1. Complexes of 3 and 4 have been fully characterized including the X-ray structure determination. The structural analysis shows that each nickel atom in 3 or 4 is bonded to two bidentate ligands L1 or L2, respectively, in a cis arrangement.

A novel potentially tridentate N-heterocyclic carbene (NHC) precursor, anionic salicylaldimine-functionalized imidazolium bromide, [3,5-tBu2-2-(HO)C6H2CHNCH2CH2(CH{NCHCHNiPr})Br] (HL·HBr, 2), was designed. The reaction of in situ-generated monoanionic tridentate salicylaldiminato-functionalized NHC LNa with Ni(PPh3)2Br2 affords a novel mono-ligand Ni(II) bromide, [3,5-tBu2-2-(O)C6H2CHNCH2CH2(C{NCHCHNiPr})]NiBr (LNiBr, 3), in good yield. Complex 3 can also be synthesized by the direct reaction of nickelocene (Cp)2Ni or bis-indenyl Ni(II) complex (Ind)2Ni with 2 in high yield via the cyclopentadiene or indene elimination reaction, respectively. Complex 3 has been fully characterized including X-ray structural determination. Preliminary study indicated that 3 shows good catalytic activity for the polymerization of styrene in the presence of NaBPh4 at 80 °C.

The reaction of (1-Et-Ind)Li (1-Et-Ind=1-ethylindenyl) with 1.81 equivalent of Ni(PPh3)2Cl2 in ether, followed by crystallization from CH2Cl2/hexane, affords (1-Et-Ind)Ni(PPh3)Cl (1) in 58% yield. Similar reaction of (1-Et-Ind)Li with 1.81 equivalent of Ni(PPh3)2Br2 in 1,2-dimethoxyethane (DME) affords (1-Et-Ind)Ni(PPh3)Br (2) in 60% yield. The reaction of complex 1 with KI in THF/acetone affords (1-Et-Ind)Ni(PPh3)I (3) quantitatively. Crystal structure analysis revealed that 2 and 3 are isomorphous. The hapticities of the indenyl ligand in these complexes are very similar and significantly distorted from an idealized η5 mode to an unsymmetrical η3 mode. The complexes are inert toward the insertion of styrene, but are able to catalyze the polymerization of styrene effectively in the presence of PPh3 and NaBPh4.

Neutral indenyl nickel complexes with the general formula (η-1-R–Ind)Ni(PPh3)Cl (R=cyclopentyl (1), benzyl (2)) have been prepared and characterized by 1H-NMR spectroscopy and single-crystal X-ray analysis. The results of X-ray crystal structural determination reveal that the hapticity of indenyl ligand in complex 1 or 2 is significantly distorted away from an idealized η5 mode to an unsymmetrical η3 mode. Furthermore, the structures of (R–Ind)Ni(PPh3)Cl exhibit a progressively more distorted coordination of the indenyl ring from cyclopentyl to benzyl. Both of them are inert toward the insertion of styrene, however, they are able to catalyze the polymerization of styrene effectively in the presence of NaBPh4 and PPh3 to give syndio-rich atactic poly(styrene) with Mw values in the range of 104. The NaBPh4·1·PPh3 system shows the higher catalytic activity than the NaBPh4·2·PPh3 system.

The International Cooperative Biodiversity Groups (ICBG) Program based at the University of Illinois at Chicago (UIC) is a program aimed to address the interdependent issues of inventory and conservation of biodiversity, drug discovery and sustained economic growth in both developing and developed countries. It is an interdisciplinary program involving the extensive synergies and collaborative efforts of botanists, chemists and biologists in the countries of Vietnam, Laos and the USA. The UIC-ICBG drug discovery efforts over the past 18 years have resulted in the collection of a cumulative total of more than 5500 plant samples (representing more than 2000 species), that were evaluated for their potential biological effects against cancer, HIV, bird flu, tuberculosis and malaria. The bioassay-guided fractionation and separation of the bioactive plant leads resulted in the isolation of approximately 300 compounds of varying degrees of structural complexity and/or biological activity. The present paper summarizes the significant drug discovery achievements made by the UIC-ICBG team of multidisciplinary collaborators in the project over the period of 1998–2012 and the projects carried on in the subsequent years by involving the researchers in Hong Kong.