7184-60-3 Usage
Description
BORRELIDIN is a novel macrolide compound that functions as a selective inhibitor of bacterial and eukaryotic threonyl-tRNA synthetase. It exhibits potent anti-angiogenic activity, modulates alternative splicing of VEGF, induces apoptosis in ALL cell lines, and triggers the unfolded protein response in oral cancer cells. BORRELIDIN is also cell permeable.
Uses
Used in Pharmaceutical Industry:
BORRELIDIN is used as an anti-angiogenic agent for its ability to prevent tube formation in rat aorta explants and induce apoptosis in endothelial cells. It also alters the splicing of VEGF mRNA, producing an antiangiogenic isoform of the growth factor.
Used in Antimalarial Drug Development:
BORRELIDIN is used as an antimalarial drug, as it effectively kills P. falciparum with an IC50 value of 1.8 nM, making it a significant lead for antimalarial discovery.
Used in Cancer Research:
BORRELIDIN is used as an apoptosis inducer in ALL cell lines and as an unfolded protein response inducer in oral cancer cells, which contributes to its potential as a therapeutic agent against cancer.
Used in Bacterial Inhibition:
Originally discovered as active against Borrelia species, BORRELIDIN is used as a selective inhibitor of bacterial and eukaryotic threonyl-tRNA synthetase, which has implications for treating bacterial infections.
At higher doses, BORRELIDIN is used as an inhibitor of cyclin-dependent kinase in yeast, resulting in growth arrest in the G1 phase, which can be beneficial in the study of cell cycle regulation and development of related therapeutics.
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.
Enantioselective total synthesis of borrelidin
Duffey, Matthew O.,LeTiran, Arnaud,Morken, James P.
, p. 1458 - 1459 (2007/10/03)
The first total synthesis of the natural product borrelidin is described. The propionate fragment of the molecule was concisely synthesized through catalytic enantioselective reductive aldol reactions, a catalytic Negishi coupling, and a catalytic directed hydrogenation. The propionate segment was then fused to the vinyl iodide fragment through a catalytic Sonogashira coupling. Subsequent catalytic hydrostannylation and catalytic cyanation allowed access to the target structure. Copyright
