85503-20-4Relevant academic research and scientific papers
Enzymatic logic of anthrax stealth siderophore biosynthesis: AsbA catalyzes ATP-dependent condensation of citric acid and spermidine
Oves-Costales, Daniel,Kadi, Nadia,Fogg, Mark J.,Song, Lijiang,Wilson, Keith S.,Challis, Gregory L.
, p. 8416 - 8417 (2007)
Petrobactin is an iron-chelating siderophore originally isolated from Marinobacter hydrocarbonoclasticus that has been shown to play an important role in growth under iron-deficient conditions and virulence of the deadly bioterrorism agent Bacillus anthracis. It has recently been shown not to bind to siderocalin, leading it to be designated as a "stealth siderophore" that can avoid the mammalian immune system. A unique combination of nonribosomal peptide synthetase (NRPS) and NRPS-independent siderophore (NIS) synthetase enzymes is known to be required for petrobactin biosynthesis in B. anthracis. Here it is shown that AsbA from B. anthracis, the first type A NIS synthetase to be biochemically characterized, catalyzes ATP-dependent regioselective condensation of citric acid with N8 of spermidine, but not with N1-(3,4-dihydroxybenzoyl)-spermidine. These results rule out a recently proposed pathway for petrobactin biosynthesis involving AsbA-catalyzed condensation of N1-(3,4-dihydroxybenzoyl)-spermidine with citric acid and show that acylation of N1 of spermidine with the 3,4-dihydroxybenzoyl group must occur after acylation of N8 of spermidine with citrate. They also provide the fundamental knowledge needed to establish a high throughput screen for inhibitors of AsbA that may provide the basis for development of new antibiotics for the treatment of deadly anthrax infections. Copyright
Total Synthesis and Biological Evaluation of Paenilamicins from the Honey Bee Pathogen Paenibacillus larvae
Bulatov, Timur,Dang, Tam,Ebeling, Julia,Genersch, Elke,Gensel, Sebastian,Koller, Timm O.,Mainz, Andi,Voigt, Kerstin,Wilson, Daniel N.,Süssmuth, Roderich D.
, p. 288 - 296 (2022/01/19)
Paenilamicins are a group of complex polycationic peptide secondary metabolites with antibacterial and antifungal activities produced by the devastating honey bee brood pathogen Paenibacillus larvae causing the lethal brood disease American Foulbrood (AFB
Design, synthesis and anticancer activity of 2-amidomethoxy-1,4-naphthoquinones and its conjugates with Biotin/polyamine
Manickam, Manoj,Boggu, Pulla Reddy,Pillaiyar, Thanigaimalai,Nam, Yeo Jin,Abdullah, Md.,Lee, Seung Jin,Kang, Jong Seong,Jung, Sang-Hun
, (2020/12/03)
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.
Naphthalene diimide-polyamine hybrids as antiproliferative agents: Focus on the architecture of the polyamine chains
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)
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.
Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives
Jagu, Elodie,Djilali, Rachid,Pomel, S??bastien,Ramiandrasoa, Florence,Pethe, St??phanie,Labru?¤re, Rapha??l,Loiseau, Philippe M.,Blonski, Casimir
, p. 207 - 209 (2015/03/05)
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).
Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives
Jagu, Elodie,Djilali, Rachid,Pomel, Sébastien,Ramiandrasoa, Florence,Pethe, Stéphanie,Labruère, Rapha?l,Loiseau, Philippe M.,Blonski, Casimir
, p. 207 - 209 (2015/04/14)
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).
New ianthelliformisamine derivatives as antibiotic enhancers against resistant gram-negative bacteria
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)
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.
Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: Design, synthesis, and validation
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
, p. 1952 - 1968 (2012/11/06)
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.
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
Chadwick, James,Jones, Michael,Mercer, Amy E.,Stocks, Paul A.,Ward, Stephen A.,Park, B. Kevin,O'Neill, Paul M.
experimental part, p. 2586 - 2597 (2010/06/16)
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
Synthesis of new alkylaminooxysterols with potent cell differentiating activities: Identification of leads for the treatment of cancer and neurodegenerative diseases
De Medina, Philippe,Paillasse, Michael R.,Payre, Bruno,Silvente-Poirot, Sandrine,Poirot, Marc
experimental part, p. 7765 - 7777 (2010/08/03)
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.
