Discovery and structure-activity relationship studies of novel tetrahydro-β-carboline derivatives as apoptosis initiators for treating bacterial infections

Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.In this paper,to discover the new bactericide candidates,we designed,prepared a new type of1,2,3,4-tetrahydro-β-carboline(THC)derivatives and evaluated the in vitro and in vivo bioactivities against the Xanthomonas oryzae pv.oryzae(Xoo),Xanthomonas axonopodis pv.citri(Xac),and Pseudomonas syringae pv.actinidiae(Psa).The in vitro bioassay results exhibited that most title molecules possessed good activity toward the three plant pathogenic bacteria,the compound A17 showed the most active against Xoo and Xac with EC50 values of 7.27 and 4.89 mg mL^(-1)respectively,and compound A8 exhibited the best inhibitory activity against Psa with EC50value of 4.87 mg mL^(-1).Pot experiments showed that compound A17 exhibited excellent in vivo antibacterial activities to manage rice bacterial leaf blight and citrus bacterial canker,with protective efficiencies of 52.67 and 79.79%at 200 mgmL^(-1),respectively.Meanwhile,compound A8 showed good control efficiency(84.31%)against kiwifruit bacterial canker at 200 mg mL^(-1).Antibacterial mechanism suggested that these compounds could interfere with the balance of the redox system,damage the cell membrane,and induce the apoptosis of Xoo cells.Taken together,our study revealed that tetrahydro-β-carboline derivatives could be a promising candidate model for novel broadspectrum bactericides.

β-Carboline alkaloids from Trigonostemon filipes and Trigonostemon lii

Sixβ-carboline alkaloids including three new ones,trifilines A-C(1-3)were isolated from Trigonostemon filipes,along with a newβ-carboline alkaloid,trigonoine C(7)isolated from Trigonostemon lii.Their structures were elucidated by extensive spectroscopic techniques.Trifilines A(1)and B(2)showed weak anti-HIV-1 activity with EC50 values of 54.61μg/mL and 9.75μg/mL,along with TI(Therapeutic index)values of 1.52 and 1.42,respectively.This is the first time to report the chemical constituents of Trigonostemon filipes.

A New β-Carboline Alkaloid and a New Derivate of Isoferulic Acid from Anemone altaica

A new β-carboline alkaloid, 4-（9H-β-carbolin-1-yl）-4-oxobutyric acid and a new derivate of isoferulic acid, （E）-3-（3-hydroxy-4-methoxyphenyl）acrylic acid carboxymethyl ester, were isolated from the roots of Anemone altaica. Their structures were determined on the basis of spectral data.

Chiral Ligands from Abrine.4. Heterocycle-Containing 1,2,3,4-Tetrahydro-β-Carboline Methyl Ester Used for Catalysis of Enantioselective Addition of Diethylzinc to Benzaldehyde

Four 1, 2,3,4-tetrahydro - β - c arboline amino acid esters with a heterocycle at the C- 1position were used as chiral ligands in the enantioselective addition reactions. The differentpositions of the heteroatoms gave different effects, and medium but opposite enantioselectivitywas recorded.

Synthesis, Characterization and X-ray Crystal Structure of 2-Benzyl-7-butoxyl-9-isobutyl-1-methyl-β-carboline Bromide

2-Benzyl-7-butoxyl-9-isobutyl-1-methyl-β-carboline bromide（H-2-65） was synthesized by the reaction of Harmine with 1-iodobutane via N9-alkylation, demethyl and N2-quaternarization to obtain the new compound. The results demonstrate that H-2-65 has more remarkable anticancer activities in vitro. The results of 1H NMR, 13 C NMR, DEPT, g COSY, g HSQC, g HMBC, MS, single-crystal X-ray diffraction and elemental analysis showed that the title compound crystallizes in the triclinic system, space group P1 with a = 9.545（5）, b = 11.724（5）, c = 11.839（6） , α = 77.530（6）, β = 87.169（6）, γ = 72.823（5）o, Z = 2, V = 1235.8（10）3, Dc = 1.294 g·cm-3, F（000） = 504, the final R = 0.0453, wR = 0.1262 and S = 1.044.

Solid Phase Synthesis of β-Carbolines

Synthesis of β-carbolines on solid phase using TCCA as the key reagent is developed.

β-Carboline alkaloids from the roots of Peganum harmala L.

This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala L.Among these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial chirality.Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-carboline.The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations.The biosynthetic pathways of 1−3 were proposed.Additionally,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was evaluated.Notably,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),respectively.Furthermore,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).

1-Methoxycarbony-β-carboline from Picrasma quassioides exerts anti-angiogenic properties in HUVECs in vitro and zebrafish embryos in vivo

Angiogenesis is a crucial process in the development of inflammatory diseases,including cancer,psoriasis and rheumatoid arthritis.Recently,several alkaloids from Picrasma quassioides had been screened for angiogenic activity in the zebrafish model,and the results indicated that 1-methoxycarbony-β-carboline(MCC) could effectively inhibit blood vessel formation.In this study,we further confirmed that MCC can inhibit,in a concentration-dependent manner,the viability,migration,invasion,and tube formation of human umbilical vein endothelial cells(HUVECs) in vitro,as well as the regenerative vascular outgrowth of zebrafish caudal fin in vivo.In the zebrafish xenograft assay,MCC inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor cells.The proteome profile array of the MCC-treated HUVECs showed that MCC could down-regulate several angiogenesis-related self-secreted proteins,including ANG,EGF,b FGF,GRO,IGF-1,PLG and MMP-1.In addition,the expression of two key membrane receptor proteins in angiogenesis,TIE-2 and u PAR,were also down-regulated after MCC treatment.Taken together,these results shed light on the potential therapeutic application of MCC as a potent natural angiogenesis inhibitor via multiple molecular targets.

Strictosidine synthase,an indispensable enzyme involved in the biosynthesis of terpenoid indole andβ-carboline alkaloids

Terpenoid indole(TIAs)andβ-carboline alkaloids(BCAs),such as suppressant reserpine,vasodilatory yohimbine,and antimalarial quinine,are natural compounds derived from strictosidine.These compounds can exert powerful pharmacological effects but be obtained from limited source in nature.the whole biosynthetic pathway of TIAs and BCAs,The Pictet–Spengler reaction catalyzed by strictosidine synthase(STR;EC:4.3.3.2)is the rate-limiting step.Therefore,it is necessary to investigate their biosynthesis pathways,especially the role of STR,and related findings will support the biosynthetic generation of natural and unnatural compounds.This review summarizes the latest studies concerning the function of STR in TIA and BCA biosynthesis,and illustrates the compounds derived from strictosidine.The substrate specificity of STR based on its structure is also summarized.Proteins that contain sixbladed four-strandedβ-propeller folds in many organisms,other than plants,are listed.The presence of these folds may lead to similar functions among organisms.The expression of STR gene can greatly influence the production of many compounds.STR is mainly applied to product various valuable drugs in plant cell suspension culture and biosynthesis in other carriers.

Studies on the Chemical Constituents of Evodia rutaecarpa [Juss] Benth

从中药吴茱萸（Ｅｖｏｄｉａｒｕｔａｅｃａｒｐａ［ｊｕｓ］Ｂｅｎｔｈ）中分离出９个吲哚类生物碱和１个芳香胺。经光谱分析鉴定其结构为：ｅｖｏｄｉａｍｉｎｅ（１），ｒｕｔａｅｃａｒｐｉｎｅ（２），ｆｏｒｍｙｌｄｉｈｙｄｒｏｒｕｔａｅｃａｒｐｉｎｅ（３），ｇｏｓｈｕｙｕａｍｉｄｅＩ（４），ｅｖｏｄｉａｍｉｄｅ（５），ｈｙｄｒｏｘｙｅｖｏｄｉａｍｉｎｅ（６），βｃａｒｂｏｌｉｎｅ（７），１，２，３，４ｔｅｔｒａｈｙｄｒｏ１ｏｘｏβｃａｒｂｏｌｉｎｅ（８），ｄｅｈｙｄｒｏｅｖｏｄｉａｍｉｎｅ（９）和Ｎｍｅｔｈｙｌａｎｔｈｒａｎｙｌａｍｉｄｅ（１０）。其中８是新的天然产物，７是首次从该属植物中分离得到。

First total synthesis of marine alkaloid hyrtiosulawesine

Hyrtiosulawesine was isolated from Indonesian specimens of the marine sponges Hyrtios erectus and H.reticulatu in 2002.We report here the first total synthesis of hyrtiosulawesine using an efficient and convenient synthetic strategy which could be widely used in the synthesis of otherβ-carboline compounds.All structures of new compounds were confirmed by 1H NMR,13C NMR and HRMS.

Ayahuasca:Uses,Phytochemical and Biological Activities

Ayahuasca(caapi,yajé),is a psychoactive brew from the Amazon Basin region of South America traditionally considered a“master plant.”It is prepared as a decoction from Banisteriopsis caapi and Psychotria viridis,which it is thought that it stimulates creative thinking and visual creativity.Native healers of the Orinoco and Amazon basins have used traditionally ayahuasca as a healing tool for multiple purposes,particularly to treat psychological disorders in the patients,with some beneficial effects experimentally and clinically validated.Recently,several syncretic religions,as the“Uniao de Vegetal”(UDV)group in Brazil,have been spread around the world.The use of ayahuasca has been popularized by internet and smart-shops,bringing the psychoactive substance to new highs,emerging new“ayahuasqueros.”Ayahuasca has alkaloids asβ-carbolines and dimethyltryptamines,which inhibit the monoamine oxidase and active the 5-HT_(2A)(5-hydroxytryptamine)receptor,respectively,resulting in hallucinations in the users.Ayahuasca induces a psychedelic change in the anteroposterior coupling of the electrophysiological brain oscillations in humans.Traditional ayahuasca beverage is generating pharmacological,commercial and spiritual interest among the scientific community,government people,and different populations worldwide.The goal of this article is to report about the uses,chemistry and biological activities of ayahuasca.

Diastereoselective synthesis of functionalized tetrahydro-γ-carbolines via a[3+3] cycloaddition of 2,2’-diester aziridines with β-(indol-2-yl)-α,β-unsaturated ketones

A Sc(OTf)3-catalyzed[3+3]cycloaddition of 2,2’-diester aziridines withβ-(indol-2-yl)-α,β-unsaturated ketones was developed,affording polysubstituted tetrahydro-y-carbolines in single diastereoisomers in good to excellent yields.