Coibamide A

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Coibamide A
Names
IUPAC name
[(2S)-1-[[(2S)-1-[[(2S)-1-[[(3S,6S,9S,12S,15S,18S,21S,22R)-15-[(2S)-butan-2-yl]-18-(methoxymethyl)-6-[(4-methoxyphenyl)methyl]-3,4,10,12,16,19,22-heptamethyl-9-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1-oxa-4,7,10,13,16,19-hexazacyclodocos-21-yl]-methylamino]-4-methyl-1-oxopentan-2-yl]-methylamino]-3-methoxy-1-oxopropan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl] (2S)-2-(dimethylamino)-3-methylbutanoate
Identifiers
3D model (JSmol)
ChemSpider
  • InChI=1S/C65H110N10O16/c1-26-40(10)52-56(77)66-41(11)57(78)70(17)47(31-36(2)3)55(76)67-46(33-44-27-29-45(89-25)30-28-44)58(79)69(16)42(12)64(85)90-43(13)53(62(83)72(19)50(35-88-24)61(82)74(52)21)75(22)59(80)48(32-37(4)5)71(18)60(81)49(34-87-23)73(20)63(84)54(39(8)9)91-65(86)51(38(6)7)68(14)15/h27-30,36-43,46-54H,26,31-35H2,1-25H3,(H,66,77)(H,67,76)/t40-,41-,42-,43+,46-,47-,48-,49-,50-,51-,52-,53-,54-/m0/s1
    Key: LVHKHLZPRPTQJG-BNLDXBMISA-N
  • CC[C@H](C)[C@H]1C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)O[C@@H]([C@@H](C(=O)N([C@H](C(=O)N1C)COC)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](COC)N(C)C(=O)[C@H](C(C)C)OC(=O)[C@H](C(C)C)N(C)C)C)C)C)CC2=CC=C(C=C2)OC)CC(C)C)C)C
Properties
C65H110N10O16
Molar mass 1287.649 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Coibamide A is an antiproliferative depsipeptide which was isolated from a marine Leptolyngbya cyanobacterium.[1] Testing of coibamide A in the National Cancer Institute in vitro 60 human tumor cell line panel (NCI-60) revealed potent anti-proliferative activity and a unique selectivity profile. Similarities between coibamide A- and apratoxin A-induced changes in cell morphology, decreases in VEGFR2 expression and macroautophagy signaling in HUVECs raise the possibility that both cyanobacterial natural products share a common mechanism of action.[2] Wild-type mouse embryonic fibroblasts were more vulnerable to coibamide A than cells lacking autophagy-related protein 5 (Atg5) that suggest coibamide A as a compound with characteristics that may utilize autophagy for pro-death signaling.[3]

Solid-phase total syntheses of highly methylated cyclic azacoibamide A and its O-desmethyl analog were achieved to improve pharmacokinetic properties of coibamide A.[4]

References

  1. ^ Medina, Rebecca A.; Goeger, Douglas E.; Hills, Patrice; Mooberry, Susan L.; Huang, Nelson; Romero, Luz I.; Ortega-Barría, Eduardo; Gerwick, William H.; McPhail, Kerry L. (2008). "Coibamide A, a Potent Antiproliferative Cyclic Depsipeptide from the Panamanian Marine Cyanobacterium Leptolyngbyasp". Journal of the American Chemical Society. 130 (20): 6324–5. doi:10.1021/ja801383f. PMC 2659736. PMID 18444611.
  2. ^ Jeffrey D. Serrill; Xuemei Wan; Andrew M. Hau; Hyo Sang Jang; Daniel J. Coleman; Arup K. Indra; Adam W. G. Alani; Kerry L. McPhail; Jane E. Ishmael (2016). "Coibamide A, a natural lariat depsipeptide, inhibits VEGFA/VEGFR2 expression and suppresses tumor growth in glioblastoma xenografts". Investigational New Drugs. 34 (1): 24–40. doi:10.1007/s10637-015-0303-x. PMID 26563191. S2CID 34252666.
  3. ^ Tan, M. (2015). Investigation of autophagy-assisted cell death in response to the cancer cell toxin coibamide A (Doctoral dissertation).
  4. ^ Sable, Ganesh A.; Park, Jaekwan; Lim, Soo-Jeong; Lim, Dongyeol (2016). "Solid-phase Total Synthesis of Amide Analogues of Coibamide A: Azacoibamide a andO-Desmethyl Azacoibamide A". Bulletin of the Korean Chemical Society. 37 (3): 330–334. doi:10.1002/bkcs.10674.
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