85503-20-4Relevant articles and documents
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
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
supporting information, (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.
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).
