셀라스트롤

Celastrol
셀라스트롤
Celastrol.svg
이름
IUPAC 이름
3-히드록시-9β,13α-디메틸-2-oxo-24,25,26-트리노롤레아나-1(10),3,5,7-테트라엔-29-oic산
선호 IUPAC 이름
(2R,4aS,6aS,12bR,14aS,14bR)-10-Hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxylic acid
기타 이름
트립테린
식별자
3D 모델(JSmol)
켐스파이더
ECHA InfoCard 100.164.266 Edit this at Wikidata
펍켐 CID
유니
  • InChI=1S/C29H38O4/c1-17-18-7-8-21-27(4,19(18)15-20(30)23(17)31)12-14-29(6)22-16-26(3,24(32)33)10-9-25(22,2)11-13-28(21,29)5/h7-8,15,22,31H,9-14,16H2,1-6H3,(H,32,33)/t22-,25-,26-,27+,28-,29+/m1/s1
    키: KQJSQWZMSAGSHN-JJWQIEBTSA-N
  • InChI=1/C29H38O4/c1-17-18-7-8-21-27(4,19(18)15-20(30)23(17)31)12-14-29(6)22-16-26(3,24(32)33)10-9-25(22,2)11-13-28(21,29)5/h7-8,15,22,31H,9-14,16H2,1-6H3,(H,32,33)/t22-,25-,26-,27+,28-,29+/m1/s1
    키: KQJSQWZMSAGSHN-JJWQIEBTBs
  • CC1=C(=O)C=C2C1=CC3=C3[C@]2(CC[C@]4([C@]@]3(CC[C@]5([C@]H]4)C[C@](CC5)(C)C(=O)C)C)C)C))o
특성.
C29H38O4
어금질량 450.619 g/19−1
외관 결정 고형
녹는점 213°C(415°F, 486K)[1]
달리 명시된 경우를 제외하고, 표준 상태(25°C [77°F], 100 kPa)의 재료에 대한 데이터가 제공된다.

셀라스트롤(Trepterine)은 트립테리지움 윌포디(Thunder god bin)와 트립테리지움 르겔리(Regel의 3윙넛)의 뿌리 추출물에서 분리된 화학 화합물이다.Celastrol은 5행성 북위 키니온으로, 키니온 메티데스 계열에 속한다.생쥐에서 셀라스트롤은 NR4A1 작용제로 염증을 완화하고 자가포화를 유도한다.[2]또한 마우스에서도 사이토카인 인터루킨-1(IL-1)의 수용체인 IL1R1의 셀라스트롤이 발현력을 증가시킨다.셀라스트롤에 노출된 IL1R1 녹아웃 생쥐는 렙틴감지 또는 비만방지 효과를 나타내지 않는다.[3]

체외 및 생체내 동물 실험에서 셀라스트롤은 항균,[4] 항산화,[5] 항염증,[6][7] 항암,[8][9][10][11][12] 살충제 활동을 보인다.렙틴의 음성 조절을 억제함으로써 생쥐에게 비만 억제 효과가 있는 것으로 나타났다.[14][15][16]셀라스트롤은 당뇨병성 신혈증에 대한 (하부하부의[17] NF-170B 억제에 의한) 항당증 효과를 가지고 있고 전신 인슐린 저항성을 향상시키는 것을 보여주었다.[18]

Celastrol은 열충격 반응을 유발하는 HSP90 체세포 단백질인 IKKα 및 β 키나제의 직접 억제, CDC37과 p23의 불활성화, 프로테아솜 함수의 억제, HSF1의 활성화 등 다중 분자 표적을 통해 IKK-NF-κB 신호를 억제한다.이용 가능한 증거는 셀라스트롤 결합이 그것의 분자 목표물에 있는 시스테인 잔류물의 티올 그룹과 일치한다는 것을 나타낸다.[19]

참조

  1. ^ Ryu YB, Park SJ, Kim YM, Lee JY, Seo WD, Chang JS, et al. (March 2010). "SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii". Bioorganic & Medicinal Chemistry Letters. 20 (6): 1873–6. doi:10.1016/j.bmcl.2010.01.152. PMC 7127101. PMID 20167482.
  2. ^ Zhang L, Wang Q, Liu W, Liu F, Ji A, Li Y (2018). "The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases". J Diabetes Res. 2018: 9363461. doi:10.1155/2018/9363461. PMC 6022324. PMID 30013988.
  3. ^ Feng X, Guan D, Auen T, Choi JW, Salazar Hernández MA, Lee J, et al. (April 2019). "IL1R1 is required for celastrol's leptin-sensitization and antiobesity effects". Nature Medicine. 25 (4): 575–582. doi:10.1038/s41591-019-0358-x. PMC 7158951. PMID 30833749.
  4. ^ Padilla-Montaño N, de León Guerra L, Moujir L (March 2021). "Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources". Foods. 10 (3): 591. doi:10.3390/foods10030591. PMC 7998816. PMID 33799720.
  5. ^ Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C (October 2001). "Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 25 (7): 1341–57. doi:10.1016/S0278-5846(01)00192-0. PMID 11513350. S2CID 21569585.
  6. ^ Kim DH, Shin EK, Kim YH, Lee BW, Jun JG, Park JH, Kim JK (September 2009). "Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii". European Journal of Clinical Investigation. 39 (9): 819–27. doi:10.1111/j.1365-2362.2009.02186.x. PMID 19549173. S2CID 205291261.
  7. ^ Venkatesha SH, Yu H, Rajaiah R, Tong L, Moudgil KD (April 2011). "Celastrus-derived celastrol suppresses autoimmune arthritis by modulating antigen-induced cellular and humoral effector responses". The Journal of Biological Chemistry. 286 (17): 15138–46. doi:10.1074/jbc.M111.226365. PMC 3083183. PMID 21402700.
  8. ^ Metselaar DS, Meel MH, Benedict B, Waranecki P, Koster J, Kaspers GJL, Hulleman E (November 2019). "Celastrol-induced degradation of FANCD2 sensitizes pediatric high-grade gliomas to the DNA-crosslinking agent carboplatin". EBioMedicine. 50: 81–92. doi:10.1016/j.ebiom.2019.10.062. PMC 6921187. PMID 31735550.
  9. ^ Lee JH, Choi KJ, Seo WD, Jang SY, Kim M, Lee BW, et al. (March 2011). "Enhancement of radiation sensitivity in lung cancer cells by celastrol is mediated by inhibition of Hsp90". International Journal of Molecular Medicine. 27 (3): 441–6. doi:10.3892/ijmm.2011.601. PMID 21249311.
  10. ^ Tiedemann RE, Schmidt J, Keats JJ, Shi CX, Zhu YX, Palmer SE, et al. (April 2009). "Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and in vivo". Blood. 113 (17): 4027–37. doi:10.1182/blood-2008-09-179796. PMC 3952546. PMID 19096011.
  11. ^ Zhu H, Liu XW, Cai TY, Cao J, Tu CX, Lu W, et al. (August 2010). "Celastrol acts as a potent antimetastatic agent targeting beta1 integrin and inhibiting cell-extracellular matrix adhesion, in part via the p38 mitogen-activated protein kinase pathway". The Journal of Pharmacology and Experimental Therapeutics. 334 (2): 489–99. doi:10.1124/jpet.110.165654. PMID 20472666. S2CID 25854329.
  12. ^ Byun JY, Kim MJ, Eum DY, Yoon CH, Seo WD, Park KH, et al. (October 2009). "Reactive oxygen species-dependent activation of Bax and poly(ADP-ribose) polymerase-1 is required for mitochondrial cell death induced by triterpenoid pristimerin in human cervical cancer cells". Molecular Pharmacology. 76 (4): 734–44. doi:10.1124/mol.109.056259. PMID 19574249. S2CID 6541041.
  13. ^ Avilla J, Teixidò A, Velázquez C, Alvarenga N, Ferro E, Canela R (January 2000). "Insecticidal activity of Maytenus species (Celastraceae) nortriterpene quinone methides against codling moth, Cydia pomonella (L.) (Lepidoptera: tortricidae)". Journal of Agricultural and Food Chemistry. 48 (1): 88–92. doi:10.1021/jf990008w. PMID 10637057.
  14. ^ 키리아코우 E, 슈미트 S, 도드 GT 등셀라스트롤은 시상하부에서 단백질 티로신 인산염 PTP1B와 TCPTP를 억제함으로써 다이어트에 의한 비만에서의 체중 감소를 촉진한다.J Medchem. 2018;61(24):11144-11157. doi:10.1021/acs.jmedchem.8b01224
  15. ^ Pfuhlmann K, Schriever SC, Baumann P, Kabra DG, Harrison L, Mazibuko-Mbeje SE, et al. (November 2018). "Celastrol-Induced Weight Loss Is Driven by Hypophagia and Independent From UCP1". Diabetes. 67 (11): 2456–2465. doi:10.2337/db18-0146. PMID 30158241.
  16. ^ Liu J, Lee J, Salazar Hernandez MA, Mazitschek R, Ozcan U (May 2015). "Treatment of obesity with celastrol". Cell. 161 (5): 999–1011. doi:10.1016/j.cell.2015.05.011. PMC 4768733. PMID 26000480.
  17. ^ Lee JH, Koo TH, Yoon H, Jung HS, Jin HZ, Lee K, Lee JJ (2006). "Inhibition of NF-κB activation through targeting IκB kinase by celastrol, a quinone methide triterpenoid". Biochemical Pharmacology. 72 (10): 1311–1321. doi:10.1016/j.bcp.2006.08.014. PMID 16984800.
  18. ^ Kim JE, Lee MH, Nam DH, Song HK, Kang YS, Lee JE, et al. (2013). "Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice". PLOS ONE. 8 (4): e62068. Bibcode:2013PLoSO...862068K. doi:10.1371/journal.pone.0062068. PMC 3637455. PMID 23637966.
  19. ^ Salminen A, Lehtonen M, Paimela T, Kaarniranta K (April 2010). "Celastrol: Molecular targets of Thunder God Vine". Biochem Biophys Res Commun. 394 (3): 439–42. doi:10.1016/j.bbrc.2010.03.050. PMID 20226165.