Kailiang Wang

Synthesis and antiviral activities of phenanthroindolizidine alkaloids and their derivatives.

Racemic phenanthroindolizidine alkaloids tylophorine, antofine, and deoxytylophorinine, and optically pure alkaloids S-(+)-tylophorine and R-(-)-tylophorine were synthesized and evaluated for their antiviral activities against tobacco mosaic virus (TMV). Further salinization modifications based on tylophorine increased stability and water solubility and improved the antiviral activity in application. The bioassay results showed that most of these synthesized compounds showed higher antiviral activity against TMV in vitro and in vivo than commercial Ningnanmycin. Especially, tylophorine salt derivatives 10, 11, 13, 17, and 22 emerged as potential inhibitors of plant virus. These findings demonstrate that these phenanthroindolizidine alkaloids and their salt derivatives represent a new template for antiviral studies and could be considered for novel therapy against plant virus infection.

Design, Synthesis, and Antiviral Evaluation of Phenanthrene-Based Tylophorine Derivatives as Potential Antiviral Agents

A series of C9-substituted phenanthrene-based tylophorine derivatives (PBTs) were designed, synthesized, and first evaluated for their antiviral activities against tobacco mosaic virus (TMV). These compounds contain a phenanthrene core structure and can be synthesized some efficiently with excellent yields compared with tylophorine alkaloid. The bioassay results show that some of these compounds exhibited higher antiviral activity against TMV in vivo than tylophorine and commercial Ningnanmycin. Especially, compounds 3, 4, 9, 13, and 16 emerged as potential inhibitors of plant virus. These new findings demonstrate that these phenanthrene-based tylophorine derivatives (PBTs) represent another new template for antiviral studies and could be considered for novel therapy against plant virus infection.

Design, Synthesis, and Biological Activities of Aromatic Gossypol Schiff Base Derivatives

A series of aromatic gossypol Schiff bases have been successfully synthesized via a feasible chemical modification. The antiviral activity against tobacco mosaic virus (TMV) of these gossypol Schiff bases has been tested for the first time. The bioassay studies indicated most of these derivatives exhibited excellent anti-TMV activity, in which o-trifluoromethylaniline Schiff base (19) displayed the best antiviral activities. Furthermore, compound 19 exhibited an eminent anti-TMV effect in the field and low toxicity to mice. These results suggest it is a promising candidate for the inhibitor of plant virus.

Synthesis and antiviral, insecticidal, and fungicidal activities of gossypol derivatives containing alkylimine, oxime or hydrazine moiety.

Gossypol is a part of the cotton plants defense system against pathogens and herbivorous insects. To discover gossypol analogs with broad spectrum and high activity, a series of gossypol alkylamine Schiff base, oxime and hydrazone derivatives were synthesised and bioassayed. The biological results indicated that most of these derivatives exhibited higher anti-TMV activity than gossypol. Interestingly, the activities of compounds 10, 15, 18, 20, 23 and 26 were much higher than that of ribavirin. Furthermore, compound 26, which was low toxicity to rat, showed better activity than control plant virus inhibitors in the field. Additionally, allyl amine Schiff base (9) displayed remarkable insecticidal activities against Mythimna separata, Helicoverpa armigera and Ostrinia nubilalis, whereas (pyridin-3-yl)methanamine Schiff base (13) showed excellent activity against Culex pipiens pallens. The fungicidal results revealed that all of compounds exhibited good activity against Physalospora piricola.

A novel tylophorine analog NK-007 ameliorates colitis through inhibition of innate immune response.

In this study, we synthesized (±)-tylophorine malate (NK-007), an analog of tylophorine (DCB3503), and analyzed its anti-inflammatory effect in vivo using a dextran sulfate sodium (DSS)-induced colitis model and an acetic acid-induced colitis model. As indicated by disease activity index (DAI) and degree of macroscopic colonic damage, NK-007 can significantly suppress colitis. To delineate the underlying mechanism, we have explored the influence of NK-007 on the production of TNF-α by murine primary bone marrow-derived dendritic cells (BMDCs) as well as monocyte/macrophage cell line Raw 264.7 triggered by lipopolysaccharide (LPS). For both types of innate immune cells, NK-007 showed a potent TNF-α inhibitory effect, and has in addition reduced the expression of IL-12 in BMDCs. Moreover, Raw cells treated with NK-007 also showed decreased phosphorylation of NF-κB, which may explain the protective immune-regulatory effect of NK-007 for experimental colitis.

Discovery and SARs of Trans-3-Aryl Acrylic Acids and Their Analogs as Novel Anti- Tobacco Mosaic Virus (TMV) Agents

A series of trans-3-aryl acrylic acids 1–27 and their derivatives 28–34 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited good antiviral activity against TMV, of which compounds 1, 5, 6, 20, 27 and 34 exhibited significantly higher activity against TMV than commercial Ribavirin both in vitro and in vivo. Furthermore, these compounds have more simple structure than commercial Ribavirin, and can be synthesized more efficiently. These new findings demonstrate that trans-3-aryl acrylic acids and their derivatives represent a new template for antiviral studies and could be considered for novel therapy against plant virus infection.

DDQ/TFA: an efficient nonmetallic reagent system for the oxidative coupling to construct phenanthrene rings

A mild synthetic method of a series of phenanthrenes with different substituents on the phenanthrene ring is described. The method involves intramolecular oxidative coupling with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)/trifluoroacetic acid(TFA) as oxidant to produce phenanthrenes in high yields and is fit for large-scale preparation. Furthermore, DDQ can be regenerated by a simple oxidation. The present approach solves a key step for the synthesis of polycyclic structures related to an alkaloid tylophorine.