Cleomiscosin A

Eur J Pharm Sci. 2012 Dec 18;47(5):952-64.

QSAR, docking and in vitro studies for anti-inflammatory activity of cleomiscosin A methyl ether derivatives.[Pubmed: 23022518]

A series of five (6a-8b) novel polyhalogenated derivatives and an interesting ester (9a) derivative have been synthesized from Cleomiscosin A methyl ether.
METHODS AND RESULTS:
All the six derivatives were subjected to in silico QSAR modeling and docking studies and later the predicted results were confirmed through in vitro experiments. QSAR modeling results showed that compounds 6a and 9a possessed anti-inflammatory activity comparable or even higher than diclofenac sodium. Docking results revealed that compounds 9a and 6a showed very good anti-inflammatory activity due to low docking energies of viz., IL6 (-92.45 and -81.993 kcal mol(-1)), TNF-α (-94.992 and -69.235 kcal mol(-1)) and IL1β (-67.462 and -65.985 kcal mol(-1)). Further all the six novel derivatives were subjected for in vitro anti-inflammatory activity using primary macrophages cell culture bioassay system. At the initial doses of 1 μg/ml and 10 μg/ml, the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were quantified from cell culture supernatant using enzyme linked immunosorbent assay (ELISA). The in vitro effect of 6a-9a on cell viability in mouse peritoneal macrophage cells isolated from mice was evaluated using MTT assay.
CONCLUSIONS:
The in silico and in vitro data suggested that all the derivatives might be considered as potential anti-inflammatory drug-like molecules.

Eur J Med Chem. 2010 Nov;45(11):5150-6.

Synthesis and anti-inflammatory activity of derivatives of coumarino-lignoid, cleomiscosin A and its methyl ether.[Pubmed: 20813432]

METHODS AND RESULTS:
Six novel Cleomiscosin A (a coumarino-lignoid), derivatives have been synthesized for the first time by using electrophilic substitution reaction to give nuclear nitrated and halogenated derivatives of Cleomiscosin A in good yields. Structures of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and Mass spectral data. Some of the synthesized derivatives were tested for in-vitro target based anti-inflammatory study using primary macrophages cell culture bioassay system.
CONCLUSIONS:
The results showed that the compounds 1a, 3a and 4a (1 and 10 μg/mL) exhibited potent anti-inflammatory activity.

Zhongguo Zhong Yao Za Zhi. 2007 Jun;32(12):1175-9.

Chemical constituents from branch of Macaranga adenantha and their TNF-alpha inhibitory activity.[Pubmed: 17802880]

To investigate the chemical constituents of the brach of Macaranga adenantha, and evaluate their TNF-alpha inhibitory activity.
METHODS AND RESULTS:
The chemical conshifuents were isolated and purified by chromatographic methods. Structures of the compounds were identified by spectroscopic methods. The TNF-alpha secretion inhibitory activity of the mouse peritoneal macrophages was evaluated by MTT methods. Ten compounds were isolated and their structures were identified as: Cleomiscosin A (1), cleomiscosin B (2), ellagic acid 4-O-alpha-D-rhamnopyranside (3), ellagic acid 4-O-beta-D-xylopyranoside (4), vanillic acid (5), (24R) -stigmast-4-en-3-one (6), (24R) -stigmast-3, 6-dione (7), (24R) -6beta-hydroxy-stigmast-4-en-3-one (8), daucosterol (9), beta-sitosteryl glucoside-6'-O-heptadecoicate (10). At a concentration of 10 micromol x L(-1), compounds 1, 3 and 4 showed inhibitory activity to TNF-alpha secretion of the mouse peritoneal macrophages with the inhibitory rates of 57.0%, 64.4%, and 57. 4%, respectively.
CONCLUSIONS:
All compounds were isolated from genus Macaranga for the first time. Compounds 1, 3, and 4 were active against TNF-alpha secretion of the mouse peritoneal macrophages. CONCLUSION: All compounds were isolated from genus Macaranga for the first time. Compounds 1, 3, and 4 were active against TNF-alpha secretion of the mouse peritoneal macrophages.

J Nat Prod. 1984 May-Jun;47(3):550-1.

Antitumor Agents, 65. Brusatol and Cleomiscosin A, Antileukemic Principles from Brucea javanica.[Pubmed: 6481366]

METHODS AND RESULTS:
Antitumor Agents, 65. Brusatol and Cleomiscosin A, Antileukemic Principles from Brucea javanica.

Arch Pharm Res. 2007 Mar;30(3):275-81.

Antioxidant activity of cleomiscosins A and C isolated from Acer okamotoanum.[Pubmed: 17424931]

Phytochemical investigation of Acer okamotoanum leaf and twig led to the isolation of two coumarinolignans, Cleomiscosin A (1) and cleomiscosin C (2).
METHODS AND RESULTS:
Here, we found that 2 dose-dependently inhibits LDL oxidation mediated by either catalytic copper ions (Cu2+) or free radicals generated with the azo compound 2,2'-azobis-(2-amidinopropane)dihydro-chloride (AAPH) with IC50s of 29.5 and 11.9 microM, respectively. By electrophoretic analysis, we also observed that 2 protects apolipoprotein B-100 (apoB-100) against Cu2+-induced fragmentation (65.3% inhibition at 5 microM). Furthermore, fluorescence analyses clearly indicated that both 1 and 2 protect against the oxidative modification of apoB-100 induced by either Cu2+ or HOCl (1, IC50s of 13.4 and 8.1 microM, respectively; 2, IC50s of 23.6 and 3.9 microM, respectively).
CONCLUSIONS:
These findings suggest that 1 and 2 could be beneficial in preventing LDL oxidation in atherosclerotic lesions.

Indian J Pharm Sci. 2010 Nov-Dec; 72(6): 759–765.

Hepatoprotective Effects and Safety Evaluation of Coumarinolignoids Isolated from Cleome viscosa Seeds.[Pubmed: 21969749 ]

The aim of the present work was to investigate the in vivo hepatoprotective potential of coumarinolignoids (Cleomiscosin A, cleomiscosin B, and cleomiscosin C) isolated from the seeds of C. viscosa. The study was performed against CCl4-induced hepatotoxicity in albino rats.
METHODS AND RESULTS:
Rats were divided into four groups. The animals of group I served as normal and was given only vehicle. Group II served as toxin control and administered with CCl4 (50% solution liquid paraffin, 2 ml/kg intraperitoneally). The animals of group III received coumarinolignoids (50 mg/kg) for six days orally as well as CCl4 (2 ml/kg) on 4th day i.p. Similarly animals of group IV received silymarin (50 mg/kg) for six days orally as well as CCl4 on 4th day i.p. On 7th day various parameters viz. serum glutamyl oxaloacetic transaminase, serum glutamyl pyruvate transaminase, serum alkaline phosphatase, serum bilirubin, liver glycogen were estimated and histopathology was performed. Additionally, acute oral toxicity of the said coumarinolignoids was carried out in swiss albino mice. The coumarinolignoids were found to be effective as hepatoprotective against CCl4-induced hepatotoxicity as evidenced by in vivo and histopathological studies in small animals. Safety evaluation studies also exhibit that coumarinolignoids are well tolerated by small animals in acute oral toxicity study except minor changes in red blood cell count and hepatic protein content at 5000 mg/kg body weight as a single oral dose.
CONCLUSIONS:
Coumarinolignoids which is the mixture of three compounds (Cleomiscosin A, cleomiscosin B and cleomiscosin C) is showing the significant protective effects against CCl4-induced hepatotoxicity in small animals and also coumarinolignoids are well tolerated by small animals in acute oral study.