- Design, synthesis and anticancer activity of 2-amidomethoxy-1,4-naphthoquinones and its conjugates with Biotin/polyamine
-
In continuation with the previous work, a series of 5-hydroxy-2-amidomethoxy-1,4-naphthoquinones were prepared to establish the structure-activity relationship studies toward anticancer activity (IC50 in μM) against three cell lines; colo205 (colon adenocarcinoma), T47D (breast ductal carcinoma) and K562 (chronic myelogenous leukemia). Among the synthesized compounds, naphthoquinone amines, 5 (0.8; 0.6; 0.8), 14 (0.8; 0.6; 0.5) and the amine precursor, 4 (1.3; 0.3; 1.0) displayed potent anticancer activities. A tumor targeting drug delivery system was achieved by synthesizing the conjugate 6 (1.4; 0.5; 1.1) of naphthoquinone-amine 5 and Biotin which also proved its potency. Finally, to introduce polyamine conjugate, spermidine was attached with 2-amidomethoxy-1,4-naphthoquinone. The naphthoquinone-spermidine conjugate 27 (1.2; 1.7; 1.7) also retained the activity. Thus, potent naphthoquinone amines were explored and Biotin/polyamine conjugate was developed as tumor targeting drug delivery system.
- Manickam, Manoj,Boggu, Pulla Reddy,Pillaiyar, Thanigaimalai,Nam, Yeo Jin,Abdullah, Md.,Lee, Seung Jin,Kang, Jong Seong,Jung, Sang-Hun
-
supporting information
(2020/12/03)
-
- A naphthalimide-polyamine conjugate preferentially accumulates in hepatic carcinoma metastases as a lysosome-targeted antimetastatic agent
-
Disseminated tumors lead to approximately 90% of cancer-associated deaths especially for hepatocellular carcinoma (HCC), indicating the imperative need of antimetastatic drugs and the ineffectiveness of current therapies. Recently polyamine derivatives have been identified as a promising prospect in dealing with metastatic tumors. Herein, a novel class of naphthalimide-polyamine conjugates 8a-8d, 13a-13c, 17 and 21 were synthesized and the mechanism was further determined. The polyamine conjugate 13b displayed remarkably elevated anti-tumor and anti-metastatic effects (76.01% and 75.02%) than the positive control amonafide (46.91% and 55.77%) at 5 mg/kg in vivo. The underlying molecular mechanism indicated that in addition to induce DNA damage by up-regulating p53 and γH2AX, 13b also targeted lysosome to modulate polyamine metabolism and function in a totally different way from that of amonafide. Furthermore, the HMGB1/p62/LC3II/LC3I and p53/SSAT/β-catenin pathways were mainly involved in the inhibition of 13b-induced HCC metastasis by targeting polyamine transporters (PTs) overexpressed in HCC. At last, 13b down-regulated the concentrations of Put, Spd and Spm by modulating polyamine metabolism key enzymes SSAT and PAO, which favored the suppression of fast growing tumor cells. Taken together, our study implies a promising strategy for naphthalimide conjugates to treat terminal cancer of HCC by targeting autophagy and tumor microenvironment with reduced toxicities and notable activities.
- Ma, Jing,Li, Linrong,Yue, Kexin,Zhang, Zhansheng,Su, Shihao,Chen, Yutong,Yu, Lu,Zhang, Pengfei,Ma, Ruijuan,Li, Yingguang,Ma, Yinxia,Jia, Huinan,Wang, Chaojie,Wang, Jiajia,Xie, Songqiang
-
-
- Naphthalene diimide-polyamine hybrids as antiproliferative agents: Focus on the architecture of the polyamine chains
-
Naphthalene diimides (NDIs) have been widely used as scaffold to design DNA-directed agents able to target peculiar DNA secondary arrangements endowed with relevant biochemical roles. Recently, we have reported disubstituted linear- and macrocyclic-NDIs that bind telomeric and non-telomeric G-quadruplex with high degree of affinity and selectivity. Herein, the synthesis, biological evaluation and molecular modelling studies of a series of asymmetrically substituted NDIs are reported. Among these, compound 9 emerges as the most interesting of the series being able to bind telomeric G-quadruplex (ΔTm = 29 °C at 2.5 μM), to inhibit the activity of DNA processing enzymes, such as topoisomerase II and TAQ-polymerase, and to exert antiproliferative effects in the NCI panel of cancer cell lines with GI50values in the micro-to nanomolar concentration range (i.e. SR cell line, GI50= 76 nM). Molecular mechanisms of cell death have been investigated and molecular modelling studies have been performed in order to shed light on the antiproliferative and DNA-recognition processes.
- Milelli, Andrea,Marchetti, Chiara,Greco, Maria Laura,Moraca, Federica,Costa, Giosuè,Turrini, Eleonora,Catanzaro, Elena,Betari, Nibal,Calcabrini, Cinzia,Sissi, Claudia,Alcaro, Stefano,Fimognari, Carmela,Tumiatti, Vincenzo,Minarini, Anna
-
p. 107 - 122
(2017/02/10)
-
- 8-polyamido dihydromyricetin derivative and preparation method and application thereof
-
The present invention discloses an 8-polyamido dihydromyricetin derivative or a pharmaceutically acceptable hydrate and salt thereof including stereoisomers or tautomers thereof. The 8-polyamido dihydromyricetin derivative has anticancer activity and can be used for anticancer treatment drugs. The invention discloses a preparation method of the 8-polyamido dihydromyricetin derivative.
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-
Paragraph 0021
(2018/03/28)
-
- METHODS OF INCREASING THE CYTOTOXICITY OF CHEMOTHERAPEUTIC AGENTS WITH MULTISUBSTRATE INHIBITORS OF HISTONE, PROTEIN-LYS, POLYAMINE ACETYLATION, AND POLYAMINE METABOLISM
-
A method of treating cancer in a subject in need thereof, comprising administering to the subject a first amount of a compound of the HAT inhibitor of the following formula: wherein R is chosen from coenzyme A, (CH2)2NHCO(CH2)2NHCOR2; (CH2)2NHCOR3; (CH2)2NHCO(CH2)2NHCOR4; R1 is H, NH2, NH, N, and R1 can optionally cyclize with at least one other X2 to form a C3-8 membered ring containing C, O, S, or N; R2 is chosen from alkyl, cycloalkyl, aryl, heteroaryl; R3 is chosen from an alkyl, cycloalkyl, aryl, heteroaryl; R4 is chosen from CH(OH)C(CH3)2CH2)OCOR2; X1 is chosen from H or can cyclize with one other X2 or R1 to form a C3-8 membered ring containing C, O, S, or N; and X2 is chosen from C, N, NH, and can optionally cyclize with at least one other X2 or R1 to form a C3-8 membered ring containing C, O, S, or N; or a pharmaceutically acceptable salt or hydrate thereof, thereby treating the cancer.
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Page/Page column 21
(2016/09/26)
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- Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives
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A structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. Among them, a spermidine derivative (compound 13) was specifically active in vitro against Leishmania donovani axenic amastigotes (IC50 at 5.4 ??M; Selectivity Index >18.5) and a spermine derivative (compound 28) specifically active against Trypanosoma brucei gambiense (IC50 at 1.9 ??M; Selectivity Index >52).
- Jagu, Elodie,Djilali, Rachid,Pomel, S??bastien,Ramiandrasoa, Florence,Pethe, St??phanie,Labru?¤re, Rapha??l,Loiseau, Philippe M.,Blonski, Casimir
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p. 207 - 209
(2015/03/05)
-
- Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives
-
A structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. Among them, a spermidine derivative (compound 13) was specifically active in vitro against Leishmania donovani axenic amastigotes (IC50 at 5.4 μM; Selectivity Index >18.5) and a spermine derivative (compound 28) specifically active against Trypanosoma brucei gambiense (IC50 at 1.9 μM; Selectivity Index >52).
- Jagu, Elodie,Djilali, Rachid,Pomel, Sébastien,Ramiandrasoa, Florence,Pethe, Stéphanie,Labruère, Rapha?l,Loiseau, Philippe M.,Blonski, Casimir
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p. 207 - 209
(2015/04/14)
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- New ianthelliformisamine derivatives as antibiotic enhancers against resistant gram-negative bacteria
-
A series consisting of ianthelliformisamimes A, B, and C as well as its synthetic analogues was prepared in high chemical yield, from 27 to 91%, using peptide coupling as the key step, and the compounds were evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives against Pseudomonas aeruginosa when combined with doxycycline was precisely evaluated utilizing bioluminescence to measure ATP efflux and fluorescence to evaluate membrane depolarization.
- Pieri, Cyril,Borselli, Diane,Di Giorgio, Carole,De Méo, Michel,Bolla, Jean-Michel,Vidal, Nicolas,Combes, Sébastien,Brunel, Jean Michel
-
p. 4263 - 4272
(2014/06/09)
-
- Syntheses of a library of molecules on the marine natural product ianthelliformisamines platform and their biological evaluation
-
Ianthelliformisamines A-C are a novel class of bromotyrosine-derived antibacterial agents isolated recently from the marine sponge Suberea ianthelliformis. We have synthesized ianthelliformisamines A-C straightforwardly by the condensation of (E)-3-(3,5-dibromo-4-methoxyphenyl)acrylic acid and the corresponding Boc-protected polyamine followed by Boc-deprotection with TFA. Further, using this reaction protocol, a library of their analogues (39 analogues) has been synthesized by employing 3-phenylacrylic acid derivatives and Boc-protected polyamine chains through various combinations of these two fragments differing in phenyl ring substitution, double bond geometry or chain length of the central spacer of the polyamine chain (shown in red color). All the synthesized compounds (ianthelliformisamines A-C and their analogues) were screened for antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. All synthetic analogues of ianthelliformisamine A showed bacterial growth inhibition against both strains (Escherichia coli and Staphylococcus aureus), having MIC values in the range of 117.8-0.10 μM, while none of the synthetic analogues of ianthelliformisamine C as well as the parent compound showed any detectable antibacterial activity. Interestingly, some of the synthetic analogues of ianthelliformisamines A and B exerted a bactericidal effect against both E. coli and S. aureus strains, decreasing viable bacterial count by 99% at concentrations as low as 2 × MIC. This journal is the Partner Organisations 2014.
- Khan, Faiz Ahmed,Ahmad, Saeed,Kodipelli, Naveena,Shivange, Gururaj,Anindya, Roy
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p. 3847 - 3865
(2014/06/09)
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- PLANT ACTIVATOR
-
A compound useful as a plant activator for activating an endogenous defense system of a plant to control disease damage is provided. A compound represented by the formula: (R3)NH—(CH2)4—N(R1)—(CH2)3—NH(R2) (one of R1 and R2 represents a linear C6-18 alkanoyl group or alkenoyl group, the other represents hydrogen atom or a protective group of amino group; and R3 represents hydrogen atom or a protective group of amino group).
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- Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: Design, synthesis, and validation
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Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μ. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.
- Corcé, Vincent,Morin, Emmanuelle,Guihéneuf, Solène,Renault, Eric,Renaud, Stéphanie,Cannie, Isabelle,Tripier, Rapha?l,Lima, Luís M. P.,Julienne, Karine,Gouin, Sébastien G.,Loréal, Olivier,Deniaud, David,Gaboriau, Fran?ois
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p. 1952 - 1968
(2012/11/06)
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- Asymmetric synthesis of bioactive hydrodibenzofuran alkaloids: (-)-lycoramine, (-)-galanthamine, and (+)-lunarine
-
Divergent route: A direct C-C bond-forming approach to the key aryl-substituted all-carbon quaternary stereogenic center present in bioactive hydrodibenzofuran alkaloids has been discovered. This approach involves an unprecedented organocatalytic enantioselective Michael addition of α-cyanoketones with acrylates (see scheme) and was used in a novel and divergent synthetic strategy for the title compounds in asymmetric fashion.
- Chen, Peng,Bao, Xu,Zhang, Le-Fen,Ding, Ming,Han, Xiao-Jie,Li, Jing,Zhang, Guo-Biao,Tu, Yong-Qiang,Fan, Chun-An
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supporting information; experimental part
p. 8161 - 8166
(2011/10/18)
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- Polyamine functionalized carbon nanotubes: Synthesis, characterization, cytotoxicity and siRNA binding
-
In this work we have synthesized a new series of cationic carbon nanotubes (CNTs) for siRNA binding. Both single- and multi-walled CNTs have been modified by addition or amidation reaction with short linear polyamine chains including putrescine, spermidin
- Singh, Prabhpreet,Samori, Cristian,Toma, Francesca Maria,Bussy, Cyrill,Nunes, Antonio,Al-Jamal, Khuloud T.,Menard-Moyon, Cecilia,Prato, Maurizio,Kostarelos, Kostas,Bianco, Alberto
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p. 4850 - 4860
(2011/10/09)
-
- Design, synthesis and antimalarial/anticancer evaluation of spermidine linked artemisinin conjugates designed to exploit polyamine transporters in Plasmodium falciparum and HL-60 cancer cell lines
-
A series of artemisinin-spermidine conjugates designed to utilise the upregulated polyamine transporter found in cancer cells have been prepared. These conjugates were evaluated against human promyelocytic leukaemia HL-60 cells and chloroquine-sensitive 3
- Chadwick, James,Jones, Michael,Mercer, Amy E.,Stocks, Paul A.,Ward, Stephen A.,Park, B. Kevin,O'Neill, Paul M.
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experimental part
p. 2586 - 2597
(2010/06/16)
-
- Synthesis of glycocinnasperimicin D
-
The first total synthesis of amino sugar antibiotic glycocinnasperimicin D (1) has been achieved by a convergent, three-component coupling strategy. The key steps involve the Heck-Mizoroki reaction by using the iodophenyl glycoside 50 and acryl amide 32 to furnish the right core structure of 1, and the construction of the urea glycoside employing the reaction of glycosyl isocyanate 8 with amino sugar 9. Glycosyl isocyanate 8 was prepared by the oxidation of isonitrile 10, which displayed excellent reactivity in the coupling event. Synthetic roadblocks, encountered during this synthetic effort, have led to the development of the α-selective, Lewis acid catalyzed phenyl glycosylation process with 2-amino-hexopyranose and a procedure for acetonide deprotection without affecting the silyl ethers.
- Nishiyama, Taihei,Kusumoto, Yoshifumi,Okumura, Ken,Hara, Kanako,Kusaba, Shohei,Hirata, Keiko,Kamiya, Yukihiro,Isobe, Minoru,Nakano, Keiji,Kotsuki, Hiyoshizo,Ichikawa, Yoshiyasu
-
supporting information; experimental part
p. 600 - 610
(2010/05/02)
-
- Synthesis of new alkylaminooxysterols with potent cell differentiating activities: Identification of leads for the treatment of cancer and neurodegenerative diseases
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We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-α-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5α-hydroxyl-6β-aminoalkylsterols is presented. Compounds were first screened for dendrite outgrowth and cytotoxicity in vitro, and two leads were selected and further characterized. 5α-Hydroxy-6β-[2- (1Himidazol-4-yl)ethylamino]cholestan-3β-ol, called dendrogenin A, induced growth control, differentiation, and the death of tumor cell lines representative of various cancers including metastatic melanoma and breast cancer. 5α-Hydroxy-6β-[3-(4-aminobutylamino)propylamino]cholest-7-en- 3β-ol, called dendrogenin B, induced neurite outgrowth on various cell lines, neuronal differentiation in pluripotent cells, and survival of normal neurones at nanomolar concentrations. In summary, we report that two new alkylaminooxysterols, dendrogenin A and dendrogenin B, are the first members of a class of compounds that induce cell differentiation at nanomolar concentrations and represent promising new leads for the treatment of cancer or neurodegenerative diseases.
- De Medina, Philippe,Paillasse, Michael R.,Payre, Bruno,Silvente-Poirot, Sandrine,Poirot, Marc
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experimental part
p. 7765 - 7777
(2010/08/03)
-
- THIAZOLIDINONE AMIDES, THIAZOLIDINE CARBOXYLIC ACID AMIDES, AND SERINE AMIDES, INCLUDING POLYAMINE CONJUGATES THEREOF, AS SELECTIVE ANTI-CANCER AGENTS
-
Substituted thiazolidinone carboxylic acid amides and substituted thiazolidine carboxylic acid amides having a structure where the various substituent groups are as defined in the specification. Methods of making these compounds, pharmaceutical compositions containing the compounds, and their use, particularly for treating or preventing cancer, are also disclosed.
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Page/Page column 5; sheet 6
(2008/12/04)
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- Cationic calix[4]arenes as anion-selective ionophores
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1,3-Alternate cationic calix[4]arene 1 proved highly selective for proton/halogens symport transport and showed antiproliferative activity against murine monocyte/macrophage J774.A1 cancer cells. The Royal Society of Chemistry.
- Izzo, Irene,Licen, Sabina,Maulucci, Nakia,Autore, Giuseppina,Marzocco, Stefania,Tecilla, Paolo,De Riccardis, Francesco
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supporting information; experimental part
p. 2986 - 2988
(2009/02/04)
-
- Anchoring cationic amphiphiles for nucleotide delivery significance of DNA release from cationic liposomes for transfection
-
We have designed and synthesized lithocholic acid-based cationic amphiphile molecules as components of cationic liposomes for gene transfection (lipofection). To study the relationship between the molecular structures of those amphiphilic molecules, particularly the extended hydrophobic appendant (anchor) at the 3-hydroxyl group, and transfection efficiency, we synthesized several lithocholic and isolithocholic acid derivatives, and examined their transfection efficiency. We also compared the physico-chemical properties of cationic liposomes prepared from these derivatives. We found that isolithocholic acid derivatives exhibit higher transfection efficiency than the corresponding lithocholic acid derivatives. This result indicates that the orientation and extension of hydrophobic regions influence the gene transfection process. Isolithocholic acid derivatives showed a high ability to encapsulate DNA in a compact liposome-DNA complex and to protect it from enzymatic degradation. Isolithocholic acid derivatives also facilitated the release of DNA from the liposome-DNA complex, which is a crucial step for DNA entry into the nucleus. Our results show that the transfection efficiency is directly influenced by the ability of the liposome complex to release DNA, rather than by the DNA-encapsulating ability. Molecular modeling revealed that isolithocholic acid derivatives take relatively extended conformations, while the lithocholic acid derivatives take folded structures. Thus, the efficiency of release of DNA from cationic liposomes in the cytoplasm, which contributes to high transfection efficiency, appears to be dependent upon the molecular shape of the cationic amphiphiles.
- Hirashima, Naohide,Minatani, Kazuhiro,Hattori, Yoshifumi,Ohwada, Tomohiko,Nakanishi, Mamoru
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p. 1117 - 1122
(2008/02/07)
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- STEROID-HORMONE CONJUGATES WITH POLYAMINES AND THEIR THERAPEUTIC USE AS ANTI-CANCER AND ANGIOSTATIC AGENTS
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Compounds of formula (I): {in which: one of R1 and R2 represents a group of formula (II): -NH-(CH2)N-NH-[(CH2)m-NH]x-[(CH2)p-NH]y (II) [where n, m and p each represents a number from 2 to 6; and x and y each represents zero or a number from 1 to 2]; and the other of R1 and R2 represents hydrogen, oxo, hydroxyl, a Cl - C6 alkanoyl group or said group of formula (II); R3 and R4 each represents oxo, hydroxy, mercapto, hydrogen, halogen, alkoxy or aryloxy; R5 represents hydrogen or methyl or is not present; the dotted line indicates a single or douse bond; and the dotted circle indicates none, one, two or three double bonds between pairs of adjacent carbon atoms}; and esters thereof are useful for the treatment or prevention of tumours and/or diabetic retinopathy.
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Page/Page column 31
(2008/06/13)
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- 7-POLYAMINOALKYL(OXY)IMINOMETHYLCAMPTOTHECINS BEARING PROTECTIVE GROUPS
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Compounds are disclosed with the general formula (I) in which the groups are as defined in the description here below and characterized by the presence of polyamine substituents on the imine/oxime residue, such amine groups being in turn protected by suitable protective groups. Said compounds are endowed with potent topoisomerase I inhibiting activity and therefore are useful as medicaments for the treatment of tumours and viral and parasite infections.
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Page/Page column 7
(2008/06/13)
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- Total Synthesis of Petrobactin and Its Homologues as Potential Growth Stimuli for Marinobacter hydrocarbonoclasticus, an Oil-Degrading Bacteria
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A modular synthesis was developed to access petrobactin, a catechol-containing siderophore isolated from Marinobacter hydrocarbonoclasticus. A range of petrobactin homologues with differing dihydroxybenzamide motifs and in one case an increased number of
- Gardner, Richard Andrew,Kinkade, Rebecca,Wang, Chaojie,Phanstiel IV, Otto
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p. 3530 - 3537
(2007/10/03)
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- Regiocontrolled synthesis of the macrocyclic polyamine alkaloid (±)-lunarine, a time-dependent inhibitor of trypanothione reductase
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A regiocontrolled synthesis of the macrocyclic polyamine alkaloid (±)-lunarine is described. The key steps involve the preparation of the differentially functionalised cis-3-oxo-8-bromo-9b-cyano-1,2,3,4,4a,9b-hexahydrobenzofuranyl tricyclic scaffold 14 wh
- Hamilton, Chris J.,Fairlamb, Alan H.,Eggleston, Ian M.
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p. 1115 - 1123
(2007/10/03)
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- Space-filling effects in membrane disruption by cationic amphiphiles
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We studied the hemolytic activity towards bovine erythrocytes of novel synthetic steroid-polyamine conjugate consisting of a rigid hydrophobic steroid unit, and a flexible hydrophilic polyamine unit connected by a linker. The steroid structure, polyamine chain length, and the presence of a hydrophobic substituent on the steroid, all influenced the activity. Analysis of the time dependence of hemolysis suggested that these structurally related cationic amphiphiles have different mechanisms of membrane perturbation. Copyright
- Fujiwara, Tomoko,Hirashima, Naohide,Hasegawa, Seiji,Nakanishi, Mamoru,Ohwada, Tomohiko
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p. 1013 - 1024
(2007/10/03)
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- Synthesis of 13C-dilabeled 4-coumaroylspermidines
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Five 13C-dilabeled constitution isomers of 4-coumaroylspermidines were prepared in nine to eleven steps: N1,4-di[(E)-4-coumaroyl]-(5,8- 13C2)spermidine (13b), N1-[(E)-4-coumaroyl]-(5,8-13C2)spermidine (17b), N1,8-di[(E)-4-coumaroyl]-(1,4-13C2)spermidine (20b), N4-[(E)-4- coumaroyl]-(1,4-13C2)spermidine (24b) and N1,4,8-tri[(E)-4-coumaroyl]- (5,8-13C2)spermidine (26). The two 13C-atoms were subsequently introduced using labeled potassium cyanide. The synthesis proceeds through stepwise construction of the polyamine backbone including protection and deprotection steps of the amino functions. Based on 1H-1H NOE interactions, the preliminary study of their binding reveals that 20b binds to tRNA in the same way as spermidine does, whereas 24b and 26 do not show any NOE effects with the tRNA protons.
- Geneste, Herve,Hesse, Manfred
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p. 15199 - 15214
(2007/10/03)
-
- Method for inhibiting angiogenesis using squalamine and squalamine steroid derivatives
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A method of inhibiting angiogenesis in a patient includes administering to the patient an effective amount of squalamine or a pharmaceutically acceptable salt of squalamine. Alternatively, a compound according to the following Formula (III) (or a pharmaceutically acceptable salt thereof) can be administered: STR1 wherein Z5 is α-H or β-H; each of the substituents Z7 is selected from the group of --H, --OH, --SH, --NH2, --F, --(C1 -C3)-alkyl, and --(C1 -C3)-alkoxy; and one of the substituents Z12 is --H and the other is --H or --OH. X' is a polyamine side chain of the formula --X1 --(CH2)p --X2 --(CH2)q --N(RII)(RIII), wherein one of X1 and X2 is --N(RIV) and the other is selected from the group of --N(RV), --O, --S, and --CH2. RIV and RV are each --H or --(C1 -C3)-alkyl, p and q are each an integer of from 0 to 5 (but both are not 0). RII and RIII in the formula for X' are each --H, --(C1 -C3)-alkyl, or --(CH2)r --N(R10)(R11) wherein r is an integer from 2 to 5 and R10 and R11 are each --H or --(C1 -C3)-alkyl. R' in Formula (III) is --H or --(C1 -C3)-alkyl, and Y' is --(C1 -C10)-alkyl, unsubstituted or substituted with --CO2 H, --OH, --NH--SO2 CF3, --SO3 H, --PO3 H2, --OSO3 H, --CF3, --F, STR2
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- Method of treating a viral infection by administering a steroid compound
-
A method of treating a viral infection includes administering an effective amount of a compound having the following structure: STR1 or a pharmaceutically acceptable salt thereof. This compound treats the viral infection by suppressing the growth of a viral target cell. As one specific example, this compound may be used to treat HIV infection.
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- Method of inhibiting the sodium/proton exchanger NHE3 and method of inhibiting growth by administering squalamine
-
Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also disclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.
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- Steroid derivatives, pharmaceutical compositions containing them, and their use as antibiotics or disinfectants
-
Compounds having a broad range of antimicrobial activity generally have a structure including asteroid nucleus with a cationic, preferably polyamine, side chain (X) and an anionic side chain (Y). The invention is also directed to compounds of the Formula III: STR1 preferably where the steroid ring nucleus is saturated; the steroid ring substituent Z5 is α-H; one Z7 is β-H and the other is α-H or α-OH; both substituents Z12 are hydrogen; X' is a polyamine side chain of the formula --NH--(CH2)p --NH--(CH2)q --N(RII)(RIII) where p and q are each independently 3 or 4, and RII and RIII are each independently hydrogen or methyl; R' is methyl; and Y' is (C1 -C10)-alkyl substituted with a group such as --CO2 H or --SO3 H.
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-
- The synthesis of p-cumaroylspermidines
-
The synthesis of three mono[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 10, 20, and 28, three bis[(E)3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 6, 16, and 25, and one tris[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidine is described.
- Hu, Wenqiag,Hesse, Manfred
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p. 548 - 559
(2007/10/03)
-
- Synthesis of philanthotoxin analogs with bulky heads including porphyrins. Self-assembly monitored by circular dichroism
-
Philanthotoxin (PhTX) analogs with bulky bis-iminodibenzyl and porphyrin head groups have been prepared. Exciton coupled CD studies show that dependent on the hydrophobicity of the head group PhTX analogs may get amphiphilic properties forming micelles in
- Huang, Danwen,Matile, Stefan,Berova, Nina,Nakanishi, Koji
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p. 723 - 736
(2007/10/03)
-
- N4-Benzoylspermidine from Oncinotis tenuiloba: Analytical Differentiation of the Three Isomeric N-Benzoylspermidines
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During the examination of extracts from Oncinotis tenuiloba STAPF a new polyamine, N4-benzoylspermidine (8), was isolated.For unambiguous structure elucidation, it was transformed into the diacetyl derivative 13, and the three possible N-benzoy
- Doll, Martin K.-H.,Guggisberg, Armin,Hesse, Manfred
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p. 1229 - 1235
(2007/10/02)
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- Regioselective synthesis of inhibitors of histone acetyl transferase covalently linking spermidine to the S-terminus of coenzyme A and fragments.
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The reaction of a bromoacetylthioester BrCH2CO-S-R (R radical in the coenzyme A series) with spermidine (Spd) derivatives is investigated and it is established that the adduct SpdCOCH2-S-R 1 is the product of the reaction.Parallel studies with model compounds show that this is a general reaction of bromoacetylthioesters.The synthesis of analogs of 1 is described and they correspond to inhibitors of the histone acetyltransferase. Key words: spermidine, coenzyme A, cysteamine, β-aletheine, enzyme inhibitors.
- Roblot, Georges,Wylde, Renee,Martin, Aimee,Parello, Joseph
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p. 6381 - 6398
(2007/10/02)
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- Facile synthesis of monoacetylated spermidines, illustrating selective deacetylation and application of a common precursor.
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The synthesis of all three monoacetylated spermidines is reported. N4-Acetylspermidine was obtained in four steps from spermidine via the triacetylated intermediate by selective deacetylation after exhaustive t-butoxycarbonylation as well as directly from
- Lurdes,Almeida,Grehn,Ragnarsson
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p. 990 - 994
(2007/10/02)
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- A Short Synthesis via a Common Intermediate of N1- and N8-Monoacylspermidine Conjugates
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N1- and N8-Substituted spermidine (1) conjugates formed with different oxygenated cinnamic acids occur in many higher plants and also in some micro-organisms.A short and efficient synthetic route to such compounds (14) -(17), (21), a
- Sundaramoorthi, Rajeswari,Fourrey, Jean-Louis,Das, Bhupesh C.
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p. 2759 - 2763
(2007/10/02)
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