Structure-activity relationships in flavonoids 4. Vinylogous chalcones and metadichalcones

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 22, No. 9, pp. 1104–1108, September, 1988.     

Structure-activity relationship in flavonoids. 9. Antiallergic activity of chalcones

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 25, No. 8, pp. 18–22, August, 1991.     

Cytotoxic chalcones and flavonoids from the leaves of Muntingia calabura

Two new dihydrochalcones, 2',4'-dihydroxy-3'-methoxydihydrochalcone, (-)-3'-methoxy-2',4',beta-trihydroxydihydrochalcone, a new flavanone, (2 S)-(-)-5'-hydroxy-7,3',4'-trimethoxyflavanone, and a new flavonol derivative, muntingone, along with sixteen known compounds, were isolated from the leaves of Muntingia calabura. The structures of these new compounds were determined using spectral analyses including extensive 2D NMR data. Among the isolates, (2 S)-5'-hydroxy-7,3',4'-trimethoxyflavanone, 4'-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, and 2',4'-dihydroxy-3'-methoxychalcone exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.     

Bioactivities of chalcones.

This review outlines the different bioactivities of a variety of chalcones. The cytotoxic, anticancer, chemopreventative and mutagenic properties of a number of chalcones are described followed by an account of various of these unsaturated ketones as antimicrobial agents. The antiviral, antiprotozoal and insecticidal activities of a variety of chalcones are reviewed as well as the enzyme-inhibitory properties and miscellaneous activities of some of these molecules.     

Antinociceptive effects of synthetic chalcones obtained from xanthoxyline

A wide variety of noxious stimuli are known to induce a sensation of pain evoked in a remote region of the body. Here, we show that chalcones can inhibit the pain provoked by the administration of an intraperitoneal acetic acid (AA). This study investigates the effects of 17 synthetic chalcones in the writhing test, a visceral pain model in mice. The majority of these compounds proved more active than some analgesic drugs, such as aspirin and acetaminophen, two reference drugs used here for comparison. Four chalcones, 9, 10, 16, and 17, were selected for more detailed studies, since they exhibited significant antinociceptive activities and chemical structures of interest. They caused dose-related inhibitions, proving about 15-, 10-, 9-, and 8-fold more active than the standard drugs. When administrated orally, only chalcone 9 proved to be effective. These chalcones might be further used as a model to obtain new and more potent analgesic drugs.     

生长抑素及类似物对大肠癌组织血管生成的调控

目的 :研究生长抑素 (somatostatin ,SS)与大肠癌组织微血管密度 (MVD)及相关因子血管内皮细胞生长因子 (VEGF)和基质金属蛋白酶抑制剂 2(TIMP 2 )表达的相关性。方法 :应用免疫组织化学S P法 ,分析 80例手术切除的新鲜大肠癌标本SS ,CD34,VEGF ,TIMP 2的变化。结果 :大肠癌组织中SS表达阳性率为 6 6 .2 5 % ,SS高表达组的大肠癌MVD的表达显著低于SS低表达组 (P <0 .0 1) ,SS表达与TIMP 2表达呈明显正相关 (P <0 .0 5 ) ,与VEGF呈显著负相关 (P <0 .0 5 )。结论 :SS及VEGF ,TIMP 2在人体大肠癌组织中的表达有一定拮抗性。SS的抑癌机制之一可能是干扰了血管生长因子的合成 ,影响了细胞内调节细胞生长信号的传递 ,从而抑制肿瘤血管的生长。     

Dietary flavonoids: intake, health effects and bioavailability.

Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Over 4000 different flavonoids have been described. They may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumour development in animal studies. An estimation of the total flavonoid intake is difficult, because only limited data on food contents are available. It is estimated that humans ingest a few hundreds of milligram per day. The average intake of the subclasses of flavonols and flavones in The Netherlands was 23 mg/day. The intake of flavonols and flavones was inversely associated with subsequent coronary heart disease in most but not all prospective epidemiological studies. A protective effect of flavonols on cancer was found in only one prospective study. Flavonoids present in foods were considered non-absorbable because they are bound to sugars as beta-glycosides. However, we found that human absorption of the quercetin glycosides from onions (52%) is far better than that of the pure aglycone (24%). Flavonol glycosides might contribute to the antioxidant defences of blood. Dietary flavonols and flavones probably do not explain the cancer-protective effect of vegetables and fruits; a protective effect against cardiovascular disease is not conclusive.     

Antiangiogenic and antivascular therapy for cancer.

The great interest in the potential antineoplastic effect of targeting tumor-associated blood vessels has generated an expanding armamentarium of therapeutic tools that include antiangiogenic compounds, aimed at preventing the formation of vessels, and antivascular compounds, targeted to the existing tumor vasculature. Following promising preclinical studies, antiangiogenic drugs have rapidly gained access to clinical trials.     

Antinociceptive properties of chalcones. Structure-activity relationships.

Eleven chalcones were prepared and tested as antinociceptive agents using the writhing test in mice. Some compounds, given intraperitoneally, caused potent and dose-related antinociception, being several times more active than some reference drugs. The results evidenced that some physico-chemical parameters are involved in the pharmacological activity. 3,4-Dichlorochalcone (2) was the most effective compound, and was also studied in another model of pain in mice, the formalin test. Here it inhibited only the inflammatory pain (second phase), being equipotent to the reference drugs.     

Cytoprotective effects of chalcones from Zuccagnia punctata and melatonin on the gastroduodenal tract in rats.

The effects of 2',4'-dihydroxychalcone and 2',4'-dihydroxy-3'-methoxychalcone from Zuccagnia punctata Cav. (Fabaceae) and melatonin administration on ethanol-induced gastroduodenal injury were investigated in rats. Both chalcones showed significant preventive effects in treatment with melatonin previous to the necrotising agent. These effects could be due, in part, to the radical scavenging activity of the melatonin.     

Cellular and physiological effects of soy flavonoids

Recent experimental and epidemiological studies have provided convincing evidence for a variety of health benefits derived from the consumption of soy and soy food products. For example, soy isoflavones are felt to protect against different cancers, cardiovascular disease, and bone loss. Many studies have demonstrated the effect of soy isoflavones on specific target molecules and signaling pathways, including but not limited to, cell proliferation and differentiation, cell cycle regulation, apoptosis, angiogenesis, cell adhesion and migration, metastasis, and activity of different enzymes. Isoflavones also share structural homologies with estrogens and are therefore classified as phytoestrogens with weak estrogenic properties. Since isoflavones bind to estrogen receptors (ER alpha and ER beta), they are considered to be possible estrogen receptor modulators. However, isoflavones can also exert biological effects independent of their phytoestrogenic activities. Recent studies suggest beneficial health effects of soy and recommend increasing the intake of isoflavone-rich soy protein to the level of intake commonly used in Asian countries.     

Antiangiogenic effects of S-nitrosocaptopril crystals as a nitric oxide donor

Angiogenesis is the formation of new capillaries from preexisting vessels by migration and proliferation of endothelial cells, which produce a cellular signaling messenger, nitric oxide (NO). The purpose of the present study was to examine the effects of exogenous NO donors on angiogenesis by using a novel crystalline NO donor, S-nitrosocaptopril. The characteristic X-ray diffraction pattern of S-nitrosocaptopril was demonstrated for the first time. On primary capillary endothelial cells pretreated with vascular endothelium growth factor (VEGF), S-nitrosocaptopril (1-500 microM), but not captopril, produced a dose-dependent inhibition of endothelial proliferation. On chick embryos of entire living eggs, gelatin sponges adsorbed with VEGF were implanted on the embryo chorioallantoic membrane to promote vascular growth activity within the sponges. Addition of S-nitrosocaptopril crystals (0.1 mg) to the gelatin sponges markedly reduced vascular density around the sponges, whereas captopril did not inhibit neovascularization. The vascular hemoglobin content surrounding each of the gelatin sponges was determined as a confirmatory test. S-nitrosocaptopril, but not captopril, significantly decreased the hemoglobin content of the embryo tissues immediately surrounding the gelatin sponges. In conclusion, S-nitrosocaptopril exerts an inhibitory effect on angiogenesis. This newly discovered function of S-nitrosocaptopril appears to be governed by distinct structural NO moiety.     

Photodimerization of heteroaryl chalcones: comparative antimicrobial activities of chalcones and their photoproducts

The heterocyclic analogues of chalcones were synthesized by Claisen Schmidt reaction of (a) benzaldehyde with 2-acetylfurane, 2-acetylpyrrole and 2-acetylthiophene and (b) acetophenone with furfural, thiophene-2-carbaldehyde and pyrrole-2-carbaldehyde. The photolysis of class (a) and (b) chalcones under UV lamp gave different products. The stereoselective photodimerization of 1-(furane-2-yl)-3-phenylprop-2-en-1-one (1), 3-phenyl-1-(1H-pyrrole-2-yl)-prop-2-en-1-one (2) gave β-truxinic type dimers, (3,4-diphenylcyclobutane-1,2-diyl)bis (furane-2-yl methanone) (7), (3,4-diphenylcyclobutane-1,2-diyl)bis ((1H-pyrrol-2-yl) methanone) (8) by syn head-to-head coupling whereas 3-phenyl-1-(thiophen-2-yl)-prop-2-en-1-one (3) gave δ-truxinic type dimers, (3,4-diphenylcyclobutane-1,2-diyl)bis (thiophen-2-yl methanone) (9) by anti head-to-head coupling. The photolytic products of 3-(furane-2-yl)-1-phenylprop-2-en-1-one (4), 1-phenyl-3-(thiophen-2-yl)-prop-2-en-1-one (5) and 1-phenyl-3-(1H-pyrrole-2-yl)- prop-2-en-1-one (6) were identified as corresponding 1,6-di(furane-2-yl)-3,4-diphenylhexa-1,5-diene-3,4-diol (10), 3,4-diphenyl-1,6-di(thiophen-2-yl)hexa-1,5-diene-3,4-diol (11) and 3,4-diphenyl-1,6-di(1H-pyrrol-2-yl)hexa-1,5-diene-3,4-diol (12) pinacol dimers. The antibacterial and antifungal activity of the precursor chalcones and the dimeric products showed antimicrobial activities of different extents with respect to individual compounds. In general, photolysis of heteroaryl chalcones causes the depletion of antimicrobial activity.