Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Org Chem. 2007 Nov 23;72(24):9298-307. doi: 10.1021/jo701559q. Epub 2007 Oct
 25.

Enantiomeric deoxycholic acid: total synthesis, characterization, and 
preliminary toxicity toward colon cancer cell lines.

Katona BW(1), Rath NP, Anant S, Stenson WF, Covey DF.

Author information:
(1)Department of Molecular Biology and Pharmacology, Division of 
Gastroenterology, Washington University in St Louis School of Medicine, St 
Louis, MO 63110, USA.

Deoxycholic acid (DCA) is an endogenous secondary bile acid implicated in 
numerous pathological conditions including colon cancer formation and 
progression and cholestatic liver disease. DCA involvement in these disease 
processes results partly from its ability to modulate signaling cascades within 
the cell, presumably through both direct receptor activation and general 
detergent mediated membrane changes. To further explore DCA induced changes in 
cell signaling, we completed a total synthesis of enantiomeric deoxycholic acid 
(ent-DCA) from achiral 2-methyl-1,3-cyclopentanedione. Using a modified method 
of the synthesis of ent-testosterone that proceeds through the 
(R)-(-)-Hajos-Parrish ketone, we have completed the successful synthesis of 
ent-DCA in 25 steps with a yield of 0.3% with all stereochemical assignments of 
the product confirmed by X-ray crystallography. Our studies toward this 
synthesis also uncovered the methodology for the development of a novel A,B-cis 
steroidal skeleton system containing a C3-C9 single bond as well as conditions 
to selectively ketalize the typically less reactive 12-carbonyl in poly-keto 
A,B-cis androgens. The critical micelle concentration (cmc) of ent-DCA, 
determined by a dye solubilization method, was identical to the cmc of natural 
DCA. Toxicity studies toward HT-29 and HCT-116 human colon cancer cell lines 
demonstrated that ent-DCA had similar effects on proliferation, yet showed a 
markedly decreased ability to induce apoptosis as compared to natural DCA.

DOI: 10.1021/jo701559q
PMID: 17958446 [Indexed for MEDLINE]


2. Biochim Biophys Acta. 2007 Dec;1770(12):1612-9. doi: 
10.1016/j.bbagen.2007.08.006. Epub 2007 Aug 25.

Peroxisome proliferator-activated receptor gamma agonist action of 
3-methyl-1,2-cyclopentanedione.

Choi SY(1), Chung JH, Kim DH, Chung SW, Kim JY, Yu BP, Chung HY.

Author information:
(1)Department of Pharmacy, College of Pharmacy, Pusan National University, San 
30, Jang-jun-dong, Geomjung-gu, Geomjung-ku, Busan, Korea.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear 
hormone receptor superfamily that plays a pivotal role in regulating 
inflammatory gene expression. The purpose of this study was to investigate the 
effects of coffee extract, 3-methyl-1,2-cyclopentanedione (3-MCP) on PPARs in 
vitro. Western blotting and luciferase assays using the PPAR response element 
(PPRE) construct revealed that 3-MCP induced PPARgamma-selective activation in 
YPEN-1 cells and that treatment with the PPARgamma selective antagonist, GW9662, 
was associated with a decrease in 3-MCP-induced PPARgamma activity. The 3-MCP 
also was shown to suppress reactive species generation and pro-inflammatory 
transcription factor NF-kappaB activity through PPARgamma activation. Theses 
results indicate that 3-MCP is a novel PPARgamma agonist and suggests that this 
agent may have a potential to minimize inflammation.

DOI: 10.1016/j.bbagen.2007.08.006
PMID: 17931788 [Indexed for MEDLINE]


3. J Agric Food Chem. 2007 Aug 8;55(16):6787-92. doi: 10.1021/jf070952p. Epub
2007  Jul 13.

3-methyl-1,2-cyclopentanedione down-regulates age-related NF-kappaB signaling 
cascade.

Chung JH(1), Choi SY, Kim JY, Kim DH, Lee JW, Choi JS, Chung HY.

Author information:
(1)College of Pharmacy, Pusan National University, Busan 609-735, Korea.

Activation of the redox-sensitive transcription factor, nuclear factor-kappa B 
(NF-kappaB), plays a central role in inflammation and aging processes by 
inducing pro-inflammatory genes. The present study was designed to unravel the 
molecular mechanisms underlying the anti-inflammation effects of 
3-methyl-1,2-cyclopentanedione (3-MCP) in coffee extracts. In particular, we 
investigated the effects of 3-MCP on the modulation of NF-kappaB signaling 
pathways and its target genes in the kidneys of aged animal rats: young (6 
months old), old (21 months old), and old 3-MCP-fed (4 and 8 mg/kg/day for 10 
days). The results strongly show that 3-MCP exerted potent anti-inflammatory 
effects, significantly reducing (i) the phosphorylation of inhibitor kappaB 
(IkappaB) and other NF-kappaB upstream events; (ii) the translocation of 
NF-kappaB into the nucleus; (iii) the expression of iNOS and COX-2; and (iv) 
pro-inflammatory genes such as VCAM-1, MCP-1, and IL-6. Furthermore, 3-MCP 
suppressed reactive oxygen species levels. Taken together, our results clearly 
demonstrate that 3-MCP modulated the age-related NF-kappaB signaling cascade and 
its pro-inflammatory genes. Therefore, 3-MCP is proposed to be an effective 
anti-inflammatory agent that can be a novel approach for the therapy of 
inflammation.

DOI: 10.1021/jf070952p
PMID: 17629301 [Indexed for MEDLINE]


4. J Pharm Pharmacol. 2002 Oct;54(10):1385-92. doi: 10.1211/002235702760345473.

Selective peroxynitrite scavenging activity of 3-methyl-1,2-cyclopentanedione 
from coffee extract.

Kim AR(1), Zou Y, Kim HS, Choi JS, Chang GY, Kim YJ, Chung HY.

Author information:
(1)College of Pharmacy, Pusan National University, Busan 609-735, Korea.

It has been known that reactive oxygen and nitrogen species such as nitric oxide 
(NO), superoxide radical (*O2-) and their byproduct peroxynitrite (ONOO-) induce 
cellular and tissue injury, ultimately resulting in several human diseases. In 
this study, we examined scavenging effects of 3-methyl-1,2-cyclopentanedione 
(MCP) from coffee extract on the reactivity of those toxic molecules. MCP 
significantly inhibited both the oxidation of 2,7-dichlorodihydrofluorescein 
diacetate (H2DCFDA) by reactive oxygen species (ROS) (mainly *O2-) from kidney 
homogenate (41% at 100 microM) and the generation of fluorescent 
4,5-diaminofluorescein (DAF-2) by NO from sodium nitroprusside (IC50 (concn 
producing 50% inhibition), 63.8 microM). More potently, however, MCP suppressed 
the oxidation of dihydrorhodamine 123 (DHR 123) to fluorescent rhodamine 123 
mediated by authentic ONOO- with an IC50 value of 3.3 microM. The neutralizing 
effect of the reactivity of ONOO- by MCP was due to electron donation, not 
nitration of the compound. Additionally, MCP also decreased ONOO- formation of 
nitrotyrosine adducts of glutathione (GSH) reductase, and consequently protected 
the enzyme activity of GSH reductase against decreasing by ONOO-, indicating 
that MCP may prevent ONOO- -induced damage of GSH reductase. Furthermore, MCP 
only weakly suppressed NO production, which is one of the upstream sources of 
ONOO- in-vivo, suggesting that NO production may be not a pharmacological target 
for MCP. Taken together, our results suggest that MCP may be regarded as a 
selective regulator of ONOO- -mediated diseases via direct scavenging activity 
of ONOO-.

DOI: 10.1211/002235702760345473
PMID: 12396301 [Indexed for MEDLINE]