- Discovery and preliminary mechanism of 1-carbamoyl β-carbolines as new antifungal candidates
-
Natural β-carboline alkaloids are ideal models for the discovery of pharmaceutically important entities. Various 1-substituted β-carbolines were synthesized from commercially inexpensive tryptophan and demonstrated significant in vitro antifungal activity against G. graminis. Significantly, compound 4m (EC50 = 0.45 μM) with carboxamide at 1-position displayed the best efficacy and nearly 20 folds enhancement in antifungal potential compared to Silthiopham (EC50 = 8.95 μM). Moreover, compounds 6, 7, and 4i exhibited excellent in vitro antifungal activities and in vivo protective and curative activities against B. cinerea and F. graminearum. Preliminary mechanism studies revealed that compound 4m caused reactive oxygen species accumulation, cell membrane destruction, and deregulation of histone acetylation. These findings indicated that 1-carbamoyl β-carboline can be selected as a promising model for the discovery of novel and broad-spectrum fungicide candidates.
- Sheng, Tao,Kong, Mengmeng,Wang, Yujie,Wu, HuiJun,Gu, Qin,Chuang, Anita Shyying,Li, Shengkun,Gao, Xuewen
-
-
Read Online
- An efficient route to 5-iodo-1-methylimidazole: Synthesis of xestomanzamine A
-
An efficient and practical route to C-5 functionalized N-methylated imidazoles is reported. 5-Iodo-1-methylimidazole was synthesized in four steps from imidazole, with complete regiospecificity, in 73% overall yield. The synthesis of xestomanzamine A, a marine natural product isolated in 1995 from an Okinawan sponge of Xestospongia sp., has been achieved using 5-iodo-1-methylimidazole in a modified Grignard reaction with a β-carboline ester moiety, in an overall yield of 59% based upon imidazole and 53% based upon tryptamine.
- Panosyan,Still
-
-
Read Online
- A pure red luminescent β-carboline-substituted biphenylmethyl radical: Photophysics, stability and OLEDs
-
Luminescent radicals, whose emission comes from the doublet exited state, have potential application in the field of organic optoelectronics. However, few radicals show luminescence at room temperature. Herein, a new pure red-emissive biphenyl-type (N-pyrido[3,4-b]indolyl)bis(2,4,6-trichlorophenyl)methyl radical (PyID-BTM) is designed and synthesized, in which the carbazole moiety of CzBTM (a previously reported biphenylmethyl radical by our group) is successfully replaced by β-carboline. Its photophysical properties, including the ground and excited states, and the radiative and non-radiative processes are systematically investigated. The photoluminescence quantum efficiency ( = 19.5%) of PyID-BTM is ten times higher than that of CzBTM ( = 2.0%) in cyclohexane. The crystal structure, magnetic properties, photostability and electroluminescence performance of PyID-BTM are studied. An optimized OLED device using PyID-BTM as an emissive dopant showed pure red emission with CIE coordinates of (0.649,0.317) and a maximum EQE of 2.8%, and the formation ratio of doublet excitons was up to 70%. This study provides a new approach for designing high-performance luminescence biphenylmethyl radicals for applications in organic electroluminescence.
- Abdurahman, Alim,Chen, Yingxin,Ai, Xin,Ablikim, Obolda,Gao, Yu,Dong, Shengzhi,Li, Bao,Yang, Bing,Zhang, Ming,Li, Feng
-
-
Read Online
- Dynamic Kinetic Resolution of Ethyl 1,2,3,4-Tetrahydro-β-carboline-1-carboxylate: Use of Different Hydrolases for Stereocomplementary Processes
-
Both enantiomers of 1,2,3,4-tetrahydro-β-carboline-1-carboxylic acid have been prepared by dynamic kinetic resolution of the corresponding ethyl ester (±)-1. CAL-B-catalysed hydrolysis of (±)-1·HCl in NH4OAc buffer (pH 8.0, 30 °C) provided amino acid (R)-2·HCl with 98 % ee and 90 % yield in 20 min. The hydrolysis with Alcalase in borate buffer (pH 8.0, 30 °C) showed S selectivity and the product (S)-2·HCl was obtained with 60 % ee and 66 % yield in 45 h. The absolute configuration of (S)-2 was determined by TDDFT electronic circular dichroism and optical rotation calculations.
- Megyesi, Rita,Mándi, Attila,Kurtán, Tibor,Forró, Enik?,Fül?p, Ferenc
-
-
Read Online
- Spiro[pyrrolidine-3, 3′-oxindoles] and their indoline analogues as new 5-HT6 receptor chemotypes
-
Synthetic derivatives of spiro[pyrrolidinyl-3, 3′-oxindole] alkaloids (coerulescine analogues) were investigated as new ligands for aminergic G-protein coupled receptors (GPCRs). The chemical starting point 2′-phenylspiro[indoline-3, 3′-pyrrolidin]-2-one scaffold was identified by virtual fragment screening utilizing ligand- and structure based methods. As a part of the hit-to-lead optimization a structure-activity relationship analysis was performed to explore the differently substituted 2′-phenyl-derivatives, introducing the phenylsulphonyl pharmacophore and examining the corresponding reduced spiro[pyrrolidine-3, 3′-indoline] scaffold. The optimization process led to ligands with submicromolar affinities towards the 5-HT6 receptor that might serve as viable leads for further optimization.
- Kelemen, ádám A.,Satala, Grzegorz,Bojarski, Andrzej J.,Keseru, Gy?rgy M.
-
-
Read Online
- Diversity-oriented reconstruction of primitive diketopiperazine-fused tetrahydro-β-carboline ring systems via Pictet-Spengler/Ugi-4CR/deprotection-cyclization reactions
-
An expedient construction of tetrahydro-β-carbolinediketopiperazine ring systems, which are present in various indole alkaloids, is documented. The synthetic strategy proceeds through a Pictet-Spengler reaction followed by an Ugi-4CR and deprotection-cyclization reactions. This is the first report of a Pre-Ugi multicomponent reaction modification using 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylic acid as the acidic partner. This novel approach provides highly diverse reconstructions of novel tetrahydro-β-carbolinediketopiperazine derivatives, which can also be used as privileged structures in medicinal chemistry.
- Khan, Irfan,Khan, Shahnawaz,Tyagi, Vikas,Chouhan, Pradeep Singh,Chauhan, Prem M. S.
-
p. 102713 - 102722
(2015)
-
Read Online
- Pityriacitrin alkaloid derivative containing acylthiourea structure as well as preparation method and application of pityriacitrin alkaloid derivative
-
The invention discloses a pityriacitrin alkaloid derivative containing an acylthiourea structure as well as a preparation method and application of the pityriacitrin alkaloid derivative, and relates to a biocide of the pityriacitrin alkaloid derivative co
- -
-
Paragraph 0032; 0034; 0039
(2021/08/21)
-
- pityriacitrin Alkaloid derivative containing acylhydrazone structure, and preparation method and application thereof
-
The pityriacitrin alkaloid derivative containing the acylhydrazone structure and a preparation method and application thereof relate to a biocide containing β - carboline and 1-position of pityriacitrin alkaloids containing an acylhydrazone structure, pit
- -
-
Paragraph 0031; 0033; 0038
(2021/09/29)
-
- Peganumine A alkaloid structure simplifier and application thereof
-
The invention discloses a Peganumine A alkaloid structure simplifier, a stereoisomer or a pharmaceutical salt thereof. The structure is shown in the following general formula: each substituent group is defined in the specification. The simplified structure of the Peganumine A alkaloid provided by the invention has a relatively obvious proliferation inhibition effect on liver cancer HepG2, lung cancer A549 and intestinal cancer HCT116, and the anti-tumor activity of part of compounds is higher than the anti-liver cancer HepG2 activity of Peganumine A reported in literatures.
- -
-
Paragraph 0037-0041
(2021/06/26)
-
- First total synthesis of the β-carboline alkaloids trigonostemine A, trigonostemine B and a new synthesis of pityriacitrin and hyrtiosulawesine
-
The total synthesis of four natural products, trigonostemine A, trigonostemine B, pityriacitrin, and hyrtiosulawesine was accomplished. The key intermediates, variously substituted 1-formyl-β-carbolines, were prepared in five steps via a novel synthetic approach using readily available starting materials. These formyl derivatives were then further transformed, providing a general route for the synthesis of the four title alkaloids. The method reported herein represents the first total synthesis of the two trigonostemines and a new pathway to pityriacitrin and hyrtiosulawesine.
- Szabó, Tímea,Hazai, Viktor,Volk, Balázs,Simig, Gyula,Milen, Mátyás
-
supporting information
p. 1471 - 1475
(2019/05/07)
-
- Novel indolizino[8,7-b]indole hybrids as anti-small cell lung cancer agents: Regioselective modulation of topoisomerase II inhibitory and DNA crosslinking activities
-
A novel series of bis(hydroxymethyl)indolizino[8,7-b]indole hybrids composed of β-carboline (topoisomerase I/II inhibition) and bis(hydroxymethyl)pyrrole (DNA cross-linking) are synthesized for antitumor evaluation. Of tumor cell lines tested, small cell
- Chang, Sue-Ming,Christian, Wilson,Wu, Ming-Hsi,Chen, Tai-Lin,Lin, Yi-Wen,Suen, Ching-Shu,Pidugu, Hima Bindu,Detroja, Dilip,Shah, Anamik,Hwang, Ming-Jing,Su, Tsann-Long,Lee, Te-Chang
-
p. 235 - 249
(2017/01/09)
-
- Design, synthesis and biological evaluation of β-carboline derivatives as novel inhibitors targeting B-Raf kinase
-
β-Carboline family of compounds is a large group of alkaloids widely distributed in nature and exhibits broad-spectrum anti-tumor activities. We designed and synthesized two series of novel 1-carboxamide- and 6-sulfonamide-substituted β-carboline derivatives 7a-p and 12a-b, and their wild type B-Raf kinase inhibitory activities were described. Most compounds showed moderate to excellent inhibitory activities. Among them, 1-carboxamide-6-(N-(3-(dimethylamino)propyl)-sulfamoyl)-β-carboline, 7e exhibited potent activity (IC50 = 1.62 μM), showing the potential for further investigation as a lead compound.
- Xin, Botao,Tang, Weifang,Wang, Yue,Lin, Guowu,Liu, Haichun,Jiao, Yu,Zhu, Yong,Yuan, Haoliang,Chen, Yadong,Lu, Tao
-
scheme or table
p. 4783 - 4786
(2012/08/13)
-
- Synthesis and structure of the β-carboline derivatives and their binding intensity with cyclin-dependent kinase 2
-
Series of 3-substituted of 6-aminosulfonyl-β-carbolines were designed and synthesized. In addition, the binding mode of these β-carboline derivatives with cyclin-dependent kinase 2 (CDK2) was studied by means of fluorescence measurements and molecular doc
- Wang, Yue,Jin, Qiaomei,Lin, Guowu,Yang, Taotao,Wang, Zhanwei,Lu, Yi,Tang, Yimin,Liu, Lifang,Lu, Tao
-
scheme or table
p. 435 - 441
(2012/05/04)
-
- Substituted tetrahydro-β-carbolines as potential agents for the treatment of human papillomavirus infection
-
The identification and optimization of a series of substituted tetrahydro-β-carbolines with potent activity against human papillomavirus is described. Structure-activity studies focused on the substitution pattern and chirality of the β-carboline ring system are discussed. Optimization of these parameters led to compounds with antiviral activities in the low nanomolar range.
- Miller, John F.,Turner, Elizabeth M.,Sherrill, Ronald G.,Gudmundsson, Kristjan,Spaltenstein, Andrew,Sethna, Phiroze,Brown, Kevin W.,Harvey, Robert,Romines, Karen R.,Golden, Pamela
-
scheme or table
p. 256 - 259
(2010/04/05)
-
- Synthetic analogs of indole-containing natural products as inhibitors of sortase A and isocitrate lyase
-
Guided by the inhibitory activities of indole-containing natural products against isocitrate lyase (ICL) from Candida albicans and sortase A (SrtA) from Staphylococcus aureus, a series of compounds structurally analogous to natural products were synthesized. Eight SrtA inhibitors and an ICL inhibitor having higher activities than the natural products were discovered by screening the enzyme inhibitory activities of synthesized compounds. Among the SrtA inhibitors discovered, six exhibited higher activities than p-hydroxymercuribenzoic acid, which suggests that these compounds have great potential as alternative antibacterial agents.
- Lee, Yeon-Ju,Han, Yu-Ri,Park, Wanki,Nam, Seo-Hee,Oh, Ki-Bong,Lee, Hyi-Seung
-
scheme or table
p. 6882 - 6885
(2010/12/24)
-
- ENZYME INHIBITORS
-
Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2is the side chain of a natural or non-natural alpha amino acid; Y is a bond, -C(=O)-, -S(=O)2-, -C(=O)O-, -C(O)NR3-, -C(=S)-NR3 , -C(=NH)NR3 or -S(=O)2NR3- wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n and p are independently 0 or 1 , Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula -X2-Q1- or -Q1-X2- wherein X2 is -O-, S- or NRA- wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, AIk1 and AIk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene ,or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (-O-), thioether (-S-) or amino (-NRA-) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl; X1 represents a bond; -C(=O); or -S(=O)2-; -NR4C(=O)-, -C(=O)NR4-, -NR4C(=O)NR5- , -NR4S(=O)2-, or -S(=O)2NR4-wherein R4 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; z is 0 or 1 ; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R1R2NH-Y-L1-X1-[CH2]Z- and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONHOH, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.
- -
-
Page/Page column 48; 49; 88
(2008/06/13)
-
- Method of suppressing appetite by administration of tetrahydro-beta-carboline derivatives
-
Compounds of formula I are useful for suppressing appetite, for altering macronutrient preferences, for suppressing obsessive-compulsive behavior, and for inhibiting cravings and substance abuse: STR1 wherein R 1 and R 3 are each independently H, hydroxy-alkyl, alpha-cyanoalkyl, SO 3 H, SO 2 NH 2, or C(O)R, where R is OH, NH 2, lower alkoxy, benzyloxy, or aliphatic amino acyl;R 2 and R 9 are each independently H, lower alkyl, benzyl, succinyl, or C(O)R 4, where R 4 is H, lower alkyl, hydrocarboxy-lower alkylene, or lower alkoxycarboxy-lower alkylene; andR 5, R 6, R 7, and R 8 are each independently H, halo, lower alkyl, hydroxy, lower alkoxy, or two adjacent radicals form methylenedioxy or ethylenedioxy;with the proviso that R 1, R 2, R 3, R 5, R 6, R 7, R 8, and R 9 are not simultaneously H.
- -
-
-
- EI and CI Mass Fragmentation of Tryptamine, Tetrahydro-β-carboline and Some of their Derivatives
-
EI and CI mass spectra of tryptamine and eleven of its derivatives, as well as those of tetrahydro-β-carboline (1,2,3,4-tetrahydro-9H-pyridoindole, THBC) and twelve of its derivatives were recorded and interpreted.An intense ion, most probably possessing a quinolinium ion structure, is produced from tryptamine derivatives by EI.The retro-Diels-Alder reaction is a prominent EI fragmentation pathway of β-carbolines (BC's), and a bulky 1-substituent is also easily split off.CI causes ammonia expulsion from tryptamine derivatives with a primary amino group in the side-chain; in the case of secondary amines and tryptophan derivatives, (MH)+ is the base peak when methane is used as the reaction gas. (MH)+ is the base peak in the CI spectra of BC derivatives, except in the case of derivatives which have a free carbonyl group, the loss of which often yields the base peak.
- Gynther, Jukka
-
p. 433 - 441
(2007/10/02)
-