Antiallergic Agents from Natural Sources 9. Inhibition of Nitric Oxide Production by Novel Chalcone Derivatives from Mallotus philippinensis (Euphorbiaceae)

Abstract

Mallotus philippinensis MUELL. ARG. (Euphorbiaceae) iswidely distributed in the forestes of Kelara. The Granular hairs on the surface of fruits is called Kamala. It has been used as a drug and dye. Earlier investigations on Kamala dye have afforded various flavonoides.2-5) Kamala powder is used as an anthelmintic and cathartic in traditional medicine. 6) Macrophages play an important role in non-specific host defense mechanisms. 7) In macrophages, bacterial LPS alone or in combination with cytokines like interferon-g (IFN-g) is one of the best-characterized stimuli to induce the transcription of genes encoding pro-inflammatory proteins, resulting in cytokine release and synthesis of enzymes such as cyclooxygenase-2 (COX-2) 8) and inducible nitric oxide synthase (iNOS). 9) NO is a short-lived bioactive molecule that participate in the physiology and pathophysiology of many systems.10) NO is synthesized in vivo from L-arginine by NOS with NADPH and oxygen as cosubstrates.11) Large amounts of NO may lead to tissue damage. In inflammatory disease such as rheumatoid arthritis, excessive NO production by activated macrophages has been observed. Therefore, it would be valuable to develop potent and selective inhibitors of NO for potential therapeutic use.Previously, we reported that mallotophilippens A and B, phloroglucinol derivatives from M. philippinensis, suppressed the NO production and iNOS gene expression. 3)In this work, we isolated three novel chalcone derivatives, 1, 2 and 3 ( Fig. 1), from the hexane-soluble fraction and investigated the inhibitory effects of those compounds on NO generation from activated macrophages. Results and DiscussionCompound 1 (Table 1), indicated a 2,2-dimethylpyran system.The arrangement of the substituents and the placement of the pyran at the 4aЈ/8aЈ positions were established from the results of the heteronuclear multiple bond connectivity (HMBC) experiments (Fig. 2). The chelated hydroxyl group in ring B showed the expected Kumage-gun, Kagoshima 891-3604, Japan. Received June 6, 2004; accepted August 27, 2004 Three novel chalcone derivatives, mallotophilippens C (1), D (2) and E (3) were isolated from the fruits of Mallotus philippinensis MUELL. ARG. These compounds were identified, using chemical and spectral data, as 1-[6-(3,7-dimethyl-octa-2,6-dienyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-3-(4-hydroxy-phenyl)-propenone, 3- (3,4-dihydroxy-phenyl)-1-[6-(3,7-dimethyl-octa-2,6-dienyl)

Prenylflavones from Psoralea corylifolia Inhibit Nitric Oxide Synthase Expression through the Inhibition of I-.KAPPA.B-.ALPHA. Degradation in Activated Microglial Cells

“…30) In order to reveal the mechanism for the inhibition of NO production, we analyzed the effects of 1 and 2 on the expression level of protein and mRNA of iNOS in LPS-activated microglia. Like the most of the flavonoids as iNOS inhibitors, 31,32) 1 and 2 suppressed the expression of iNOS protein and mRNA dose dependently. Since the activation of NF-kB has been known to be important for iNOS induction, 21) we examined the effects of 1 and 2 on the I-kB-a.…”

Novel, Complex Flavonoids from Mallotus philippensis (Kamala Tree)

“…Some cognates have also been found in the pericarps of Mallotus japonicus [7] [8], and they showed cytotoxic activity towards KB L-5178Y cell lines. In the case of rottlerin (1), an inhibitory effect towards protein kinase C was reported [9], and prenylated chalcones are known to inhibit nitric oxide (NO) production [6].…”

Efficient Synthesis of Biologically Interesting Natural Pyranochalcones from Mallotus Philippensis and Their Unnatural Derivatives

“…The spectral data for the synthetic materials 2 and 3 were in agreement with those reported in the literature. 1,7 Similarly, treatment of 22-24 with concentrated HCl (10 drops) in methanol at room temperature for 5 h gave the unnatural products 5-7 in 61, 76 and 58% yield, respectively. Scheme 2 shows retrosynthetic approaches for synthesizing the natural red compound (4) and its unnatural derivatives 8-11.…”

“…1 Extracts from the fruits and bark of the plant have been shown to possess antioxidant, 2 antiulcer, 2 anti-tumor, 3 cytotoxic, 4 and antiallergic 5 activities. Kamara, a red powder consisting of the glandular hairs from this plant, has been used in traditional medicines as an anthelmintic and cathartic.…”