11076-19-0 Usage
Description
Bongkrekic acid (11076-19-0) is a p potent inhibitory ligand of the mitochondrial adenine nucleotide translocase (ANT).1?Inhibits mitochondrial permeability transition pore opening.2,3?Delivery of bongkrekic acid to the mitochondria prevents apoptosis in HeLa cells.4
Uses
Bongkrekic acid solution has been used as an adenine nucleotide translocator (ANT) inhibitor to find out a different approach for the inhibition of oxidative phosphorylation in intact T98G cells. It has also been used as an inhibitor of the permeabilization transition pore complex (PTPC) pore and a tool to explore the role of PTPC in induction of apoptosis.
Definition
ChEBI: A tricarboxylic acid that is docosa-2,4,8,10,14,18,20-heptaenedioic acid substituted at positions 2 ,5 and 17 by methyl groups, at positions 6 by a methoxy group and at position 20 by a carboxymethyl group.
Biochem/physiol Actions
An antiapoptotic agent, it protects against NMDA receptor induced neuronal apoptosis,- extends cell survival in cells undergoing apoptosis following infection with viral vectors and abrogates apoptosis induced by hydrogen peroxide in T-cells. It is an inhibitor of adenine nucleotide translocase, which is a component of the mitochondrial permeability transition (MPT) pore complex. Bongkrekic acid prevents mitochondrial depolarization, swelling, rupture of mitochondrial outer membrane, and release of apoptogenic proteins such as cytochrome c. This phenomenon was observed during staurosporine induced apoptosis in Jurkat cells, in HepG2 undergoing apoptosis following TNF-α and ethanol.
Enzyme inhibitor
This toxic tricarboxylic acid (FWfree-acid = 486.61 g/mol; CAS 11076-19-0), produced Pseudomonas cocovenenans, is a potent competitive inhibitor of the mitochondrial ATP-ADP translocator, effectively blocking nucleotide binding to the carrier. The name is derived from bongkrek, a moldy coconut product produced in Indonesia. The toxin accumulates when P. cocovenenans outgrows the mold. Klingenberg et al. investigated bongkrekate binding to mitochondrial membrane to examine the reorienting site mechanism. The inferred mode of inhibition requires bongkrekate to bind to the single carrier site only from the inner face of the mitochondrial membrane (i.e., the matrix side)). They confirmed the pH-dependent accumulation of [3H]bongkrekate inside the mitochondria which superimposes onto the binding at carrier sites. By breaking the membrane with Lubrol or sonication, binding to the carrier sites could be titrated, and a Kd value of approximately 5 x 10–8 M was determined. The presence of ADP or ATP increases the amount of binding but does not alter the Kd. [35S]Atractylate is displaced by [3H]bongkrekate at a 1:1 molar ratio; this displacement is dependent on ADP concentration with the Km = 0.5 x 10–6 M. See also Atractyloside The isomer known as isobongkrekic acid, which has a cis-double bond at the dicarboxylic acid end of the molecule, has similar biological activity. Target(s): Adenine nucleotide translocator, ADP/ATP carrier; ATPase; bromelain, stem; papain; ficain, or ficin.
References
1) Ziegler?et al. (1993),?The adenine nucleotide translocase modulates oligomycin-induced quenching of pyranine fluorescence in submitochondrial particles; J. Biol. Chem.,?268?25320
2) Marchetti?et al. (1996),?Mitochondrial permeability transition triggers lymphocyte apoptosis; J. Immunol.,?157?4830
3) Zamzami?et al. (1996),?Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis; FEBS Lett.,?384?53
4) Yamada?et al. (2013),?Mitochondrial delivery of bongkrekic acid using a MITO-Porter prevents the induction of apoptosis in human HeLa cells; J. Pharm. Sci.,?102?1008
Check Digit Verification of cas no
The CAS Registry Mumber 11076-19-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,1,0,7 and 6 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 11076-19:
(7*1)+(6*1)+(5*0)+(4*7)+(3*6)+(2*1)+(1*9)=70
70 % 10 = 0
So 11076-19-0 is a valid CAS Registry Number.
InChI:InChI=1/C28H38O7/c1-21(15-18-24(19-26(29)30)20-27(31)32)13-11-9-7-5-6-8-10-12-14-25(35-4)22(2)16-17-23(3)28(33)34/h6,8-12,15-19,21,25H,5,7,13-14,20H2,1-4H3,(H,29,30)(H,31,32)(H,33,34)/b8-6+,11-9-,12-10+,18-15-,22-16-,23-17+,24-19+
11076-19-0Relevant articles and documents
Lanquin et al.
, p. 2323,2325 (1976)
Efficient Total Synthesis of Bongkrekic Acid and Apoptosis Inhibitory Activity of Its Analogues
Matsumoto, Kenji,Suyama, Masaki,Fujita, Satoshi,Moriwaki, Takuya,Sato, Yukiko,Aso, Yoshifumi,Muroshita, Satoshi,Matsuo, Hiroshi,Monda, Keishi,Okuda, Katsuhiro,Abe, Masato,Fukunaga, Hiroyuki,Kano, Arihiro,Shindo, Mitsuru
, p. 11590 - 11602 (2015/08/03)
Bongkrekic acid (BKA), isolated from the bacterium Burkholderia cocovenenans, is an inhibitor of adenine nucleotide translocator, which inhibits apoptosis, and is thus an important tool for the mechanistic investigation of apoptosis. An efficient total synthesis of BKA has been achieved by employing a three-component convergent strategy based on Kocienski-Julia olefination and Suzuki-Miyaura coupling. It is noteworthy that segment B has been prepared as a new doubly functionalized coupling partner, which contributes to shortening of the number of steps. Torquoselective olefination with an ynolate has also been applied for the efficient construction of an unsaturated ester. Furthermore, it is revealed that 1-methyl-2-azaadamantane N-oxyl is an excellent reagent for final oxidation to afford BKA in high yield. Based on the total synthesis, several BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the apoptosis inhibitory activity of BKA. More easily available BKA analogues with potent apoptosis inhibitory activity were also developed. Stripped BKA: The highly efficient second-generation total synthesis of bongkrekic acid (BKA), an apoptosis inhibitor, has been developed. The synthesis features a three-component convergent strategy based on a Kocienski-Julia olefination and Suzuki-Miyaura coupling. The structure-activity relationship (SAR) is also examined for the first time (see scheme).
Total synthesis of the anti-apoptotic agents Iso- And bongkrekic acids
Francais, Antoine,Leyva, Antonio,Etxebarria-Jardi, Gorka,Ley, Steven V.
supporting information; experimental part, p. 340 - 343 (2010/03/25)
(Figure presented) The first convergent total synthesis of isobongkrekic acid is reported involving three different stereospecific palladium cross-couplings for the formation of the diene units. Access to bongkrekic acid by this route is also demonstrated. These syntheses involve the formation of several potentially general building blocks.
Efficient synthesis of bongkrekic acid. Three-component convergent strategy
Sato, Yukiko,Aso, Yoshifumi,Shindo, Mitsuru
scheme or table, p. 4164 - 4166 (2009/12/01)
An efficient total synthesis of the apoptosis inhibitor bongkrekic acid was accomplished using a three-component convergent strategy involving a Kocienski-Julia olefination and a Suzuki-Miyaura coupling, in which the longest linear sequence was 18 steps and proceeded in 6.4% overall yield. The torquoselective olefination also contributed to the shortening of the synthesis.
