Borrelidin

Borrelidin
Identifiers
  • (1R,2R)-2-[(2S,4E,6Z,8R,9S,11R,13S,15S,16S)-7-Cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic acid
CAS Number
PubChem CID
UNII
ECHA InfoCard100.242.694 Edit this at Wikidata
Chemical and physical data
FormulaC28H43NO6
Molar mass489.653 g·mol−1
3D model (JSmol)
  • C[C@H]1C[C@H](C[C@@H]([C@H](/C(=C\C=C\C[C@H](OC(=O)C[C@@H]([C@H](C1)C)O)[C@@H]2CCC[C@H]2C(=O)O)/C#N)O)C)C
  • InChI=InChI=1S/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

Borrelidin is an 18-membered polyketide macrolide derived from several Streptomyces species. First discovered in 1949 from Streptomyces rochei,[1] Borrelidin shows antibacterial activity by acting as an inhibitor of threonyl-tRNA synthetase and features a nitrile moiety, a unique functionality in natural products.[2],[3] Borrelidin also exhibits potent angiogenesis inhibition, which was shown in a rat aorta matrix model.[4] Other studies have been performed to show that low concentrations of borrelidin can suppress growth and induce apoptosis in malignant acute lymphoblastic leukemia cells.[5] Borredlidin's antimalarial activity has also been shown in vitro and in vivo.[6]

  1. ^ Berger J, Jampolsky LM, Goldberg MW (July 1949). "Borrelidin, a new antibiotic with antiborrelia activity and penicillin enhancement properties". Archives of Biochemistry. 22 (3): 476–8. PMID 18134558.
  2. ^ Hütter R, Poralla K, Zachau HG, Zähner H (March 1966). "[Metabolic products of microorganisms. 5l. On the mechanism of action of borrelidin-inhibition of the threonine incorporation in sRNA]". Biochemische Zeitschrift. 344 (2): 190–6. PMID 4860826.
  3. ^ Paetz W, Nass G (June 1973). "Biochemical and immunological characterization of threonyl-tRNA synthetase of two borrelidin-resistant mutants of Escherichia coli K12". European Journal of Biochemistry. 35 (2): 331–7. doi:10.1111/j.1432-1033.1973.tb02843.x. PMID 4577856.
  4. ^ Wakabayashi T, Kageyama R, Naruse N, Tsukahara N, Funahashi Y, Kitoh K, Watanabe Y (August 1997). "Borrelidin is an angiogenesis inhibitor; disruption of angiogenic capillary vessels in a rat aorta matrix culture model". The Journal of Antibiotics. 50 (8): 671–6. doi:10.7164/antibiotics.50.671. PMID 9315080.
  5. ^ Habibi D, Ogloff N, Jalili RB, Yost A, Weng AP, Ghahary A, Ong CJ (August 2012). "Borrelidin, a small molecule nitrile-containing macrolide inhibitor of threonyl-tRNA synthetase, is a potent inducer of apoptosis in acute lymphoblastic leukemia". Investigational New Drugs. 30 (4): 1361–70. doi:10.1007/s10637-011-9700-y. PMID 21678129. S2CID 25124274.
  6. ^ Azcárate IG, Marín-García P, Camacho N, Pérez-Benavente S, Puyet A, Diez A, Ribas de Pouplana L, Bautista JM (June 2013). "Insights into the preclinical treatment of blood-stage malaria by the antibiotic borrelidin". British Journal of Pharmacology. 169 (3): 645–58. doi:10.1111/bph.12156. PMC 3682711. PMID 23488671.