Showing papers by "Yuxiu Liu published in 2016"

Design, Synthesis, and Biological Activities of Spirooxindoles Containing Acylhydrazone Fragment Derivatives Based on the Biosynthesis of Alkaloids Derived from Tryptophan.

Abstract: On the basis of the biosynthesis of alkaloids derived from tryptophan and considering the wide use of spirooxindole in drug molecular design, a series of novel spirooxindole derivatives containing an acylhydrazone moiety were designed, synthesized, and first evaluated for their biological activities. The results of bioassays indicated that the target compounds possessed good activities against tobacco mosaic virus (TMV); especially compound 4, containing a tert-butyl at the benzene ring, exhibited the best antiviral activity in vitro and inactivation, curative, and protection activities in vivo (48.4%, 58 ± 0.4, 55.2 ± 2.3, and 49.7 ± 1.1% at 500 μg/mL, respectively) compared with ribavirin (38.2, 36.4 ± 0.2, 37.5 ± 0.2, and 36.4 ± 0.1% at 500 μg/mL, respectively) and harmine (44.6, 40.5 ± 0.2, 38.6 ± 0.8, and 42.4 ± 0.6% at 500 μg/mL, respectively). At the same time, these compounds exhibited fungicidal activity selectively against certain fungi; most of these derivatives exhibited >60% fungicidal activi...

Design, Synthesis, Acaricidal/Insecticidal Activity, and Structure–Activity Relationship Studies of Novel Oxazolines Containing Sulfone/Sulfoxide Groups Based on the Sulfonylurea Receptor Protein-Binding Site

Abstract: Enormous compounds containing sulfone/sulfoxide groups have been used in a variety of fields, especially in drug and pesticide design. To search for novel environmentally benign and ecologically safe pesticides with unique modes of action, a series of 2,4-diphenyl-1,3-oxazolines containing sulfone/sulfoxide groups as chitin synthesis inhibitors (CSIs) were designed and synthesized on the basis of the sulfonylurea receptor protein-binding site for CSIs. Their structures were characterized by (1)H and (13)C nuclear magnetic resonance and high-resolution mass spectrometry. The acaricidal and insecticidal activities of the new compounds were evaluated. It was found that most of the target compounds displayed wonderful acaricidal activities against spider mite (Tetranychus cinnabarinus) larvae and eggs. Especially compounds I-4, II-3, and II-4 displayed higher activities than commercial etoxazole at a concentration of 2.5 mg L(-1). Some target compounds exhibited insecticidal activities against lepidopteran pests. The present work demonstrated that these compounds containing sulfone/sulfoxide groups could be considered as potential candidates for the development of novel acaricides in the future.

Discovery of Topsentin Alkaloids and Their Derivatives as Novel Antiviral and Anti-phytopathogenic Fungus Agents.

Abstract: Topsentin alkaloids and their derivatives were designed, synthesized, and characterized on the basis of NMR and mass spectroscopy. The antiviral activities against tobacco mosaic virus (TMV) and anti-phytopathogenic fungus activities of these alkaloids were evaluated for the first time. Alkaloids 1c, 1e, 2b, and 2d displayed significantly higher antiviral activities against TMV than Ribavirin, emerging as new lead compounds for anti-TMV research. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these alkaloids displayed broad-spectrum fungicidal activities. Topsentin derivative 2d with 4–5 mg/kg EC50 values against Sclerotinia sclerotiorum (Lib.), Rhizoctonia solani (Kuhn), and Botrytis cinerea (Pers.) emerged as a new lead compound for fungicidal research. Current studies provide support for the application of topsentin alkaloids as novel agrochemicals.

Copper‐Catalyzed Trifluoromethylation of Acrylamides Coupled with Indole Dearomatization: Access to Trifluoromethyl‐Substituted Spiro[indole‐3,3′‐pyrrolidine] Derivatives

Abstract: A copper-catalyzed cascade reaction involving trifluoromethylation of acrylamides coupled with ring closure and indole dearomatization is reported. This facile transformation was highly regioselective and proceeded under mild conditions, allowing efficient access to trifluoromethyl-substituted spiro[indole-3,3′-pyrrolidine] derivatives, which are of increasing interest to the pharmaceutical industry.

Copper‐Catalyzed Trifluoromethylation and Bicyclizations of 1,7‐Enynes Leading to Fused Polycycles

Abstract: A series of trifluoromethyl-containing heterocycles, like indene and dihydroquinolinone or dihydrocoumarin-fused tetracyclic compounds have been prepared using copper-catalyzed cascade reaction of benzene-tethered 1,7-enynes. A study of the mechanism indicated that radical trifluoromethylation and sequential 6-exo-dig/5-endo-trig bicyclization processes were involved in this protocol. Moreover, some selected products showed certain fungicidal activities against 14 kinds of plant fungi which means that these functionalized tetracyclic compounds might be used in the agrochemical field.

Antiviral mechanism study of gossypol and its Schiff base derivatives based on reactive oxygen species (ROS)

Abstract: A series of amino acid gossypol Schiff bases were designed, synthesized and evaluated for their anti-TMV activities, and a new method of preparing hydrophilic amino acid gossypol Schiff bases, which are difficult to prepare using existing methods, was developed. Most of these compounds displayed good activities. Structure–activity relationship studies revealed that both the carboxy group and R group in amino acids are important to their anti-TMV activities. Further mechanism studies based on ROS-producing ability indicated that the O2˙− production rates of gossypol Schiff bases showed a positive correlation with their anti-TMV activity, suggesting that O2˙− is more important than H2O2 at the primary stage of TMV inoculation. However, the gossypol Schiff bases derived from D and L-amino acids, respectively, showed different anti-TMV activities (4 > 16, 6 > 17, 7 > 18, 11 > 19) although they had the same ROS-producing abilities. Both the D and L-amino acid gossypol Schiff bases stimulate O2˙− and H2O2 production in tobacco leaves. The current study provides fundamental support for the development of gossypol alkaloids as potential inhibitors of plant viruses.

First Discovery of Polycarpine, Polycarpaurines A and C, and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents.

Abstract: Marine natural products polycarpine, polycarpaurines A and C, and their derivatives were designed, synthesized, and characterized on the basis of 1H NMR and mass spectroscopy. The antiviral and antiphytopathogenic fungus activities of these alkaloids were first evaluated. Polycarpine derivative 1g displayed excellent in vivo antiviral activity against TMV (inactivation inhibitory effect, 57%/500 μg mL–1 and 19%/100 μg mL–1; curative inhibitory effect, 62%/500 μg mL–1 and 23%/100 μg mL–1; and protection inhibitory effect, 56%/500 μg mL–1 and 29%/100 μg mL–1), which is evidently higher than the activity of ribavirin (inactivation inhibitory effect, 37%/500 μg mL–1 and 9%/100 μg mL–1; curative inhibitory effect, 36%/500 μg mL–1 and 13%/100 μg mL–1; and protection inhibitory effect, 39%/500 μg mL–1 and 17%/100 μg mL–1), thus emerging as a new lead compound for antiviral research against TMV. Fungicidal testing in vitro showed that most of the compounds displayed good fungicidal activity against plant pathogen...

Design, synthesis, antiviral activity and mode of action of phenanthrene-containing N-heterocyclic compounds inspired by the phenanthroindolizidine alkaloid antofine

Abstract: BACKGROUND The phenanthroindolizidine alkaloid antofine and its analogues have excellent antiviral activity against tobacco mosaic virus (TMV). To simplify the structure and the synthesis of the phenanthroindolizidine alkaloid, a series of phenanthrene-containing N-heterocyclic compounds (compounds 1 to 33) were designed and synthesised, based on the intermolecular interaction of antofine and TMV RNA, and systematically evaluated for their anti-TMV activity. RESULT Most of these compounds exhibited good to reasonable anti-TMV activity. The optimum compounds 5, 12 and 21 displayed higher activity than the lead compound antofine and commercial ribavirin. Compound 12 was chosen for field trials of antiviral efficacy against TMV, and was found to exhibit better activity than control plant virus inhibitors. Compounds 5 and 12 were chosen for mode of action studies. The changes in fluorescence intensity of compounds 5 and 12 on separated TMV RNA showed that these small molecules can also bind to TMV RNA, but the mode is very different from that of antofine. CONCLUSION The compounds combining phenanthrene and an N-heterocyclic ring could maintain the anti-TMV activity of phenanthroindolizidines, but their modes of action are different from that of antofine. The present study lays a good foundation for us to find more efficient anti-plant virus reagents. © 2015 Society of Chemical Industry

Design, synthesis, insecticidal activity, and structure-activity relationship (SAR): studies of novel triazone derivatives containing a urea bridge group based on transient receptor potential (TRP) channels

Abstract: Numerous compounds containing urea bridge and biurea moieties are used in a variety of fields, especially as drugs and pesticides. To search for novel, environmentally benign and ecologically safe pesticides with unique modes of action, four series of novel triazone analogues containing urea, thiourea, biurea, and thiobiurea bridge, respectively, were designed and synthesized, according to various calcium ion channel inhibitors which act on transient receptor potential protein. Their structures were characterized by [Formula: see text] NMR, [Formula: see text] NMR, and HRMS. The insecticidal activities of the new compounds were obtained. The bioassay results indicated that compounds containing a thiourea bridge and a thiobiurea bridge exhibited excellent insecticidal activities against bean aphid. Specifically, compounds [Formula: see text], [Formula: see text], and [Formula: see text] exhibited 85, 90, and 95 % activities, respectively, at 10 mg/kg. Compounds [Formula: see text] (30 %), [Formula: see text] (35 %), [Formula: see text] (30 %), and [Formula: see text] (40 %) exhibited the approximate aphicidal activity of pymetrozine (30 %) at 5 mg/kg. In addition, some target compounds exhibited insecticidal activities against lepidopteran pests. From a molecular design standpoint, the information obtained in this study could help in the further design of new derivatives with improved insecticidal activities.

Skeletal modifications of β-carboline alkaloids and their antiviral activity profile.

Abstract: To study the effect of the variation of fused ring size and substitution on the antiviral activity of [Formula: see text]-carboline alkaloids, four types of structurally novel [Formula: see text]-carboline alkaloids analogues, with indole-fused six- to nine-membered-rings motifs, were designed, synthesized, and evaluated for the inhibition of tobacco mosaic virus (TMV). Bioassay results indicated that most of these analogues had significant anti-TMV activity; especially I-14 (54 [Formula: see text] 3 % at 500 [Formula: see text]g/mL in vitro; 51 [Formula: see text] 2, 45 [Formula: see text] 2, and 42 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo), II-4 (53 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vitro; 49 [Formula: see text] 2, 57 [Formula: see text] 2, and 48 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo), and II-8 (48 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vitro; 53 [Formula: see text] 2 %, 56 [Formula: see text] 2 %, and 46 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo), which were more potent vs. TMV than was ribavirin (36 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vitro; 37 [Formula: see text] 2, 41 [Formula: see text] 2, and 38 [Formula: see text] 1 % at 500 [Formula: see text]g/mL in vivo). The size of the fused ring has important effects on anti-TMV potency, which may be ascribed to conformational differences. The X-ray structures of I-1, I-6, II-8, and III show differing conformational preferences. The most potent compounds can be used as leads for further optimization as antiphytoviral agents.

Copper-Catalyzed Trifluoromethylation of Acrylamides Coupled with Indole Dearomatization: Access to Trifluoromethyl-Substituted Spiro[indole-3,3′-pyrrolidine] Derivatives.

Abstract: A copper-catalyzed cascade reaction involving trifluoromethylation of acrylamides coupled with ring closure and indole dearomatization is reported. This facile transformation was highly regioselective and proceeded under mild conditions, allowing efficient access to trifluoromethyl-substituted spiro[indole-3,3′-pyrrolidine] derivatives, which are of increasing interest to the pharmaceutical industry.

Direct C—H Allylation of N‐Acyl/Sulfonyl Tetrahydroisoquinolines and Analogues.

Abstract: A highly efficient direct C-H allylation reaction at the α position of N-acyl/sulfonyl tetrahydroisoquinolines under mild conditions was developed. The reaction was also suitable for allylation of other protected nitrogen-containing heterocycles. Several interesting transformations of the products into valuable synthetic intermediates are featured with the successful total synthesis of (±)-crispine A.