Synthesis and Anti-tumor Activity of Novel Amide Derivatives of Ursolic Acid

Ursolic acid was modified at C3 and C28 position to obtain fourteen derivatives including twelve novel compounds, and their chemical structures were characterized by IR, ^1H NMR and MS. Cell growth inhibitory effects of the derivatives against Hela cell were evaluated by MTT assay. All these derivatives were found to have stronger cell growth inhibitory than their parent compound, ursolic acid. The derivatives with a substituted acetyl group at C3 hydroxyl group show better activities than those with an unsubstituted hydroxyl group.

CoMFA Study on Anti-proliferative Activity of Fluoroquinolone Amide Derivatives

The in vitro anti-proliferative activity(pICi,i=hp,ca,hl)of fluoroquinolone(rhodanineα,β-unsaturated ketone)amide compounds,referred to as“fluoroquinolone amide derivatives(FQADs)”towards Hep-3B,Capan-1 and HL60 cells,was studied by the 3D-QSAR method of comparative molecular field analysis(CoMFA).Based on the training set of 14 compounds,the prediction model was established,which was further verified by the test set of 5 compounds with template molecule included.It is found that steric and electrostatic fields contribute 66.8%and 33.2%to pIChp,61.4%and 38.6%to pICca,and 61.5%and 38.5%to pIChl,respectively.The Rcv 2(i.e,cross-validation coefficient)is 0.324,0.381,and 0.421 for pIChp,pICca,and pIChl,respectively,while the corresponding R2(i.e,non-cross-validation coefficient)all reach 0.999.Then,the models were employed to estimate the activities of the training and test compounds,and the results show that the stability and predictability of developed models are very satisfactory.According to the contour maps of steric and electronic fields,bulky groups linked to 2-,3-,4-positions of phenyl ring,and electropositive groups near the 4-position and electronegative groups far away may increase the anti-proliferative activity.Using the information provided by the 3D contour maps,four new FQADs owing higher antiproliferative activity were designed,but their effectiveness should be further tested by experiments.

Synthesis and insecticidal evaluation of novel sulfide-containing amide derivatives as potential ryanodine receptor modulators

With the aim of discovering new bioactive pesticides for crop protection,a series of novel sulfidecontaining amide derivatives A were efficiently synthesized via a strategy of modifying the“amide”structure of anthranilic diamide insecticides.The single-crystal structures of A2-3 and A4-5 were firstly reported.The bioassay results showed that most of the synthesized compounds display moderate to high insecticidal activities.Particularly,some sulfone-containing compounds,e.g.,A2-3,A3-3 and A6-3,not only possessed favorable lethality rate(50%–100%)against P.xylostella at a concentration of 0.1 mg/L,but also held good activities towards a variety of agricultural pests such as M.separata,C.pipiens pallen,H.armigera and O.nubilalis;the larvicidal activities of A4-1 and A6-1 towards P.xylostella were close to that of chlorantraniliprole at 0.01 mg/L.The calcium imaging experiments revealed that the representative compounds A2-3 and A6-3 are potential ryanodine receptor(RyR)modulators.The structure–activity relationships were discussed in detail.These results provide useful information for further design and development of novel insecticides.

Synthesis,insecticidal activities,and SAR studies of novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives

Diamide compounds such as chlorantraniliprole,a famous anthranilic diamide insecticide targeting the insect ryanodine receptor(Ry R),have received continuous attention in pesticide research during the past 15 years owing to their excellent insecticidal potentials.With the aim of discovering new heterocyclic pesticides used for crop protection,based on the structural information of compound M from the reported pharmacophore-based virtual screening for Ry R insecticides and diamide compound,a series of new heterocyclic mono-,di-,and tri-amide derivatives containing piperazine moiety have been synthesized in this paper.The new compounds were identified and confirmed by melting point,^(1)H NMR,^(13)C NMR and HRMS.Compound M was firstly validated for insecticidal activities,and the new synthesized compounds were all made comprehensive insecticidal evaluations against diamondback moth and oriental armyworm.The bioassay results showed that some of the compounds exhibit favorable insecticidal potentials,particularly some novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives such as 8 g,14 a,15 a,15 g,15 i,15 j,15 k,15 l,and 15 m could be used as new insecticidal leading structures for further study(e.g.,towards diamondback moth,15i-15 m LC_(50):0.0022-0.0081 mg/L).The structure-activity relationships of the compounds discussed in detail provide useful guidance for further design and development of new insecticides.

Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-L-homocysteine hydrolase inhibitors

A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosylL-homocysteine hydrolase（SAHase） inhibitory activity. Among these compounds, 8b,8m, 8r and 8w showed better or similar inhibitory effects compared to the positive control aristeromycin. These results provide a novel lead for the discovery of more potent non-adenosine analogs as SAHase inhibitors.

Synthesis, In vitro Coagulation Activities and Molecular Docking Studies on Three L-Histidine Amide Derivatives

Three novel L-histidine amide derivatives were synthesized and the corresponding chemical structures were characterized by means of melting point analysis, IR, MS, ^1H NMR as well as ^13C NMR. The coagulation activities of the compounds were evaluated by an MOE（molecular operating environment） docking technique and coagulation test. The results obtained from molecular docking show that the interactions between the compounds and thrombin exhibit procoagulant activity in combination with an improved combinatory effect. Moreover, the results of in vitro coagulation tests show that the L-histidine amide derivatives feature coagulant activities in common coagulation pathways. Compared with the blank control group, the optimal shortening rates of compounds 1-3 were 39.08%（0.5 mmol/L）, 22.94%（1.0 mmol/L） and 15.38%（0.0625 mmol/L）, respectively.

Antibacterial Activity of Novel 18β-Glycyrrhetinic Hydrazide or Amide Derivatives

Through a facile structural modification on the natural bioactive ingredient 18β-glycyrrhetinic acid(GA),a series of novel GA hydrazide or amide derivatives was obtained,and their final molecular frameworks were characterized by NMR and HRMS analysis.Antibacterial bioassays revealed that some of the GA hydrazide or amide derivatives were able to suppress the growth of three tested plant pathogens.Particularly,compound 3c exhibited excellent in vitro activity against Xanthomonas oryzae pv.Oryzae(Xoo),Pseudomonas syringae pv.actinidiae(Psa),and Xanthomonas axonopodis pv.citri(Xac),providing the EC_(50) values of 5.89,16.1,and 3.64µg/mL,respectively.The data were better than those of the positive controls thiodiazole copper(92.7,77.8,and 89.9µg/mL,respectively)and bismerthiazol(31.1,125.6,and 77.4µg/mL,respectively).In addition,in vivo experiments suggested that,compared with thiodiazole copper(41.93%and 39.73%,respectively),compound 3c exerted prominently curative and protective activities against rice bacterial leaf blight at 200µg/mL with the control effects of 52.36%and 51.40%,respectively.Given these obtained results,GA hydrazide or amide derivatives could serve as the feasible leads for exploring highly bioactive substrates.

Synthesis and Spectroscopic Study of Coumarin Derivatives

Five new coumarin amide derivatives were synthesized with coupling reagent,the structures of which were characterized by IR,1H NMR,13C NMR,MS and element analysis.Their spectral properties were studied in dichloromethane,in N,N-dimethylformamide（DMF） and in solid state.Solvent polarity has less influence on the UV-Vis maximum absorption at about 430 nm.The maximum emission wavelengths change from 464 nm to 474 nm in dichloromethane,from 476 nm to 482 nm in DMF and from 521 nm to 548 nm in solid state,respectively.The fluorescence intensities of compounds 8 and 9 were extremely strong in solvents or in solid state.Compounds 8 and 9 exhibited high fluorescenct quantumn yields in solution compared to compounds 4 ＂7.The fluorescence lifetimes of all the compounds in solvents were measured.

Design and synthesis of DPP-4 inhibitor for the treatment of type 2 diabetes

An efficient stereoselective synthesis of the rigid aza-bicyclo[3.2.0]heptane scaffold has been developed to provide 2-cyano-pyrrolidine alpha-amino amide 1 as DPP-4 inhibitor.

Synthesis and biological activity of novel N-(3-furan-2-yl-1-phenyl-1H-pyrazol-5-yl) amides derivatives

A series of novel N-（3-furan-2-yl-l-phenyl-lH-pyrazol-5-yl） amides derivatives were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR and HRMS. All title compounds were evaluated for their herbicidal and antifungal activities. Preliminary bioassay results indicated that the title compounds showed good to moderate herbicidal activity at 1000 mg/L. Compound 6q presented the best activity against Digitaria sanguinalis （L） Scop., Amaranthus retroflexus L. and Arabidopsis thaliana with an inhibition degree of five. Compound 6d also showed an inhibition degree of five against D. sanguinalis. In addition, at 50 mg/L, most compounds exhibited good in vitro antifungal activity against Sclerotinia sclerotiorum, with compound 6c showing over 90% antifungal activity against S. sclerotiorum and Pellicularia sasakii.

Construction of the Molecular Structure Model of the Zhaotong Lignite Using Simulation and Experiment Data

Aiming to better understand the physiochemical properties of lignite, we select Zhaotong lignite as object and adopt simulation and experiment data to construct its molecular structure. Firstly, the important parameters including carbon skeleton, valence state and functional group of the sample are obtained by ultimate analysis, 13 C NMR, XPS and Py-GC/MS. Results indicate that the ratio of aromatic carbon and aromatic bridge carbon to surrounding carbon of the sample are 40.32% and 0.14, respectively. Such results imply that the aromatic structure of the sample is dominated by benzene and naphthalene. Moreover, the ratio of aliphatic carbon is 51.55%, and the aliphatic structure is mainly comprised by methyl, methylene, quaternary carbon and oxygen-aliphatic carbon. Oxygen atoms principally exist in ether, carbonyl and carboxyl groups, of which ether accounts for 70.2%. Additionally, the contents of pyridine, pyrrole and quaternary nitrogen are 25.2%, 46.3% and 13.0%, respectively. Based on the aforementioned results, the molecular structure model of Zhaotong lignite is constructed by the method of computer-aided molecular design. Subsequently, the molecular formula of Zhaotong lignite is calculated as C;H;O;N;. Finally, in order to verify the reasonability of the constructed model, the 13 C NMR of the molecular structure model is simulated by employing the basis set of GIAO/6-31G at the Gaussian 09 computing platform. These simulated results agree well with the experimental ones, which suggests that the molecular structure model of Zhaotong lignite is accurate and reasonable.