7184-60-3 Usage
Description
Borrelidin (7184-60-3) ia a novel macrolide which inhibits bacterial and eukaryotic threonyl-tRNA synthetase.1 Displays potent anti-angiogenic activity (IC50=0.8 nM) and induces the collapse of newly formed capillary tubules.2 Modulates alternative splicing of VEGF in favor of anti-angiogenic isoforms.3 Induces apoptosis in ALL cell lines.4 Induces unfolded protein response in oral cancer cells.5 Cell permeable.
Uses
Different sources of media describe the Uses of 7184-60-3 differently. You can refer to the following data:
1. Borrelidin is an unusual nitrile-containing metabolite isolated from Streptomyces. Originally discovered as active against Borrelia species, borrelidin has since found a role as a selective inhibitor of bacterial and eukaryal threonyl-tRNA synthetase. More recent research has found that borrelidin is a very potent angiogenesis inhibitor and induces apoptosis of the capillary tube-forming cells. Borrelidin is an important lead for antimalarial discovery, displaying activity against drug-resistant Plasmodia.
2. Borrelidin is a secondary metabolite produced by Streptomyces and other bacteria. It displays potent antiangiogenic activity, preventing tube formation in rat aorta explants (IC50 = 0.8 nM) and inducing apoptosis in endothelial cells. Borrelidin also alters the splicing of VEGF mRNA, producing an antiangiogenic isoform of the growth factor. It has long been known as a powerful inhibitor of both eukaryotic and bacterial threonyl tRNA synthetase. Borrelidin is also an effective anti-malarial drug, as it kills P. falciparum with an IC50 value of 1.8 nM. At higher doses, it inhibits cyclin-dependent kinase in yeast (IC50 = 24 μM), resulting in growth arrest in the G1 phase.
Definition
ChEBI: A macrolide that is isolated from several Streptomyces species and displays antibiotic, antineoplastic and antimalarial properties.
General Description
Chemical structure: macrolide
Biochem/physiol Actions
Borrelidin is a potent angiogenesis inhibitor that induces apoptosis in capillary tube-forming cells. Also displays antimalarial activity against drug-resistant Plasmodia. Antimicrobial and selective threonyl t-RNA synthetase inhibitor.
References
References/Citations
1) Ruan et al. (2005), A unique hydrophobic cluster near the active site contributes to differences in borrelidin inhibition among threonyl-tRNA synthetases; J. Biol. Chem., 280 571
2) Kawamura et al. (2003), Anti-angiogenesis effects of borrelidin are mediated through distinct pathways: threonyl-tRNA synthase and caspases are independently involved in suppression of proliferation and induction of apoptosis in endothelial cells; J. Antibiot., 56 709
3) Woolard et al. (2011) Borrelidin modulates the alternative splicing of VEGF in favour of anti-angiogenic isoforms; Chem. Soc. 2011 273
4) Habibi et al. (2012), Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthase, is a potent inducer of apoptosis in acute lymphoblastic leukemia; Invest. New Drugs, 30 1361
5) Sidhu et al. (2015), Borrelidin Induces the Unfolded Protein Response in Oral Cancer Cells and Chop-Dependent Apoptosis; ACS Med. Chem. Lett., 6 1122
Check Digit Verification of cas no
The CAS Registry Mumber 7184-60-3 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 7,1,8 and 4 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 7184-60:
(6*7)+(5*1)+(4*8)+(3*4)+(2*6)+(1*0)=103
103 % 10 = 3
So 7184-60-3 is a valid CAS Registry Number.
InChI:InChI=1/C28H43NO6/c1-17-12-18(2)14-20(4)27(32)21(16-29)8-5-6-11-25(22-9-7-10-23(22)28(33)34)35-26(31)15-24(30)19(3)13-17/h5-6,8,17-20,22-25,27,30,32H,7,9-15H2,1-4H3,(H,33,34)/b6-5+,21-8-/t17-,18+,19-,20-,22+,23+,24-,25-,27+/m0/s1
7184-60-3Relevant articles and documents
Total synthesis of borrelidin
Nagamitsu, Tohru,Takano, Daisuke,Marumoto, Kaori,Fukuda, Takeo,Furuya, Kentaro,Otoguro, Kazuhiko,Takeda, Kazuyoshi,Kuwajima, Isao,Harigaya, Yoshihiro,Omura, Satoshi
, p. 2744 - 2756 (2008/02/05)
(Chemical Equation Presented) The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is macrocyclization at C11-C12 for the construction of an 18-membered ring after esterification between two segments. A detailed examination of the macrocyclization led us to the samarium(II) iodide-mediated intramolecular Reformatsky-type reaction as the most efficient synthetic approach. The two key segments were synthesized through regioselective methylation, directed hydrogenation, stereoselective Reformatsky-type reaction, and MgBr2·Et2O-mediated chelation-controlled allylation.
Total synthesis of (-)-borrelidin
Nagamitsu, Tohru,Takano, Daisuke,Fukuda, Takeo,Otoguro, Kazuhiko,Kuwajima, Isao,Harigaya, Yoshihiro,Omura, Satoshi
, p. 1865 - 1867 (2007/10/03)
Matrix presented. The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is Sml2-mediated intramolecular Reformatsky-type reaction for macrocyclization after esterification between two segments. The two key segments were synthesized through chelation-controlled carbotitanation, chelation-controlled hydrogenation, stereoselective Reformatsky reaction, and MgBr2·Et2O-mediated chelation-controlled allylation.
Application of Conformation Design in Acyclic Stereoselection: Total Synthesis of Borrelidin as the Crystalline Benzene Solvate
Hanessian, Stephen,Yang, Yang,Giroux, Simon,Mascitti, Vincent,Ma, Jianguo,Raeppel, Franck
, p. 13784 - 13792 (2007/10/03)
The total synthesis of (-)-borrelidin (treponemycin), a structurally distinct 18-membered macrolide antibiotic, has been achieved. It was isolated as the crystalline benzene solvate, and its structure was confirmed by a single-crystal X-ray analysis. The deoxypropionate subunit consisting of four alternating C-methyl groups with a C4-C10 syn/syn/anti orientation was elaborated by a new method of iterative cuprate additions to acyclic α,β-unsaturated esters relying on two consequtive 1,3-inductions and starting with D-glyceraldehyde as the chiral progenitor. The unique Z/E cyanodiene unit was obtained as a single isomer by application of the Still-Gennari olefination protocol. The γ-hydroxycyclopentane carboxylic acid subunit was prepared from L-malic acid utilizing a sequential introduction of C-vinyl and C-allyl groups, capitalizing on 1,2-induction in an acyclic α,β-unsaturated ester and carbocyclization by a Grubbs ring closure metathesis reaction. The prevalence of 1,3-syn-disposed deoxypropionate triads in the cuprate additions is rationalized on the basis of minimized syn-pentane interactions in the transition states. A virtual diamond lattice was used as a visual tool to portray the low-energy conformations of the acyclic substrates, and corroborated by 1H NMR homodecoupling studies.
