New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6-(3-Halogenated phenyl-2-propen-1-oyl)-2(3H)-benzoxazolones

In this study, novel halogenated chalcones, 6-(3-halogenated phenyl-2-propen-1-one)-2(3H)-benzoxazolones ( 2a – n ), were synthesized for the first time (except 2a ), and their chemical structures were characterized by ¹H nuclear magnetic resonance (NMR), ¹³C NMR, and high-resolution mass spectrometry spectra. Cytotoxic activities and carbonic anhydrase (CA) inhibitory effects of the compounds were studied to identify new possible drug candidate molecules. Cytotoxicity results pointed out that compound 2m , 6-[3-(3-bromophenyl)-2-propenoyl]-2(3H)-benzoxazolone, had the highest cytotoxicity (CC₅₀) and potency selectivity expression (PSE) values. Thus, compound 2m can be considered as a lead compound of the series in terms of cytotoxicity. When the CA inhibition results of the compounds were evaluated, it was found that the K_i values of the compounds ranged from 30.5 ± 11.3 to 65.5 ± 25.6 µM toward hCA I, and they ranged from 7.3 ± 1.8 to 58.8 ± 12.3 µM toward hCA II. However, the K_i values of the reference drug, acetazolamide (AZA), were 30.2 ± 7.8 and 4.4 ± 0.6 μM toward hCA I and hCA II, respectively. According to the results obtained, compounds 2a – n had lower K_i values than AZA, whereas compounds 2a , 2b , 2e – g , 2l , and 2n had similar K_i values, compared with AZA. So, the compounds 2a , 2b , 2e – g , 2l , and 2n can be considered as lead molecules of this series for further considerations.     

The Effect of (E)-1-(4’-aminophenyl)-3-phenylprop-2-en-1-one on MicroRNA-18a,Dicer1, and MMP-9 Expressions against DMBA-Induced Breast Cancer

Background: Most of breast cancer patients are estrogen receptor alpha-positive and have high resistance and side effect of chemotherapeutic drug. Therefore, discovering an effective anticancer agent is needed. This research explored the effect of (E)-1-(4’-aminophenyl)-3-phenylprop-2-en-1-one (APE) on miR-18a, Dicer1, and MMP-9 expressions. Methods: Twenty four female Sprague-Dawley rats were invetigated in this study. The rats were divided into 6 groups of 4. G1 was considered as normal rat. G2, G3, T1, T2, and T3 were given DMBA 20 mg/kgBW twice a week for 5 weeks to induce mammary cancer. After being affiliated with cancer, G2 was given vehicle and G3 was treated with tamoxifen. T1, T2, and T3 were treated with APE intraperitoneally everyday for 21 days at doses of 5, 15, and 45 mg/kgBW/day, respectively. Blood plasma was collected to measure miR-18a expression using qRT-PCR. Mammary tissues were also collected to determine Dicer1 and MMP-9 expressions by using  immunohistochemistry. Results: The results showed significant down-regulation of miR-18a relative expression and up-regulation of Dicer1 expression in G3 and T1 compared to G2 (P<0.05). MMP-9 expression has significant decrease in T1 compared to G2 (P<0.05). Conclusion: APE can decrease miR-18a and MMP-9 expressions and increase Dicer1 expression in rat mammary cancer. Therefore, this compound could be a candidate of novel anticancer.     

The behavior of some chalcones on acetylcholinesterase and carbonic anhydrase activity

Carbonic anhydrase (CA) has a key role in respiration, carbon dioxide and bicarbonate transport. Acetylcholinesterase (AChE) is a serine hydrolase and mostly abundant at neuromuscular junctions and cholinergic brain synapses. Inhibitors of these enzymes could aid in illuminating the role in disease processes. In this study, we separately purified CA I and CA II from human erythrocytes. The purity of the enzymes was showed by SDS-PAGE analysis. We also investigated the inhibition of seven chalcones toward hCA I, hCA II, and AChE. The chalcones were effective inhibitors of the cytosolic CA isoforms (hCA I and hCA II) and AChE with K_i values in the range of 1.83–7.05?μM for hCA I, 0.59–5.50?μM for hCA II, and 0.61–86.11?μM for AChE. All compounds were showed competitive inhibition aganist both enzymes. These compounds can be a potent inhibitor of AChE enzyme and both cytosolic CA isoenzymes which are commonly used in the pharmaceutical and medical industries.     

Novel 3,4-Methylenedioxybenzene Scaffold Incorporated 1,3,5-Trisubstituted-2-pyrazolines: Synthesis,Characterization and Evaluation for Chemotherapeutic Activity

A series of novel 3, 4-methylenedioxybenzene scaffold incorporated 1,3,5-trisubstituted-2-pyrazoline derivatives was synthesised as potent antitubercular agents via chalcone intermediates by reaction with hydrazines. The structures of the compounds were confirmed by IR, 1HNMR, 13CNMR and mass spectral data. The novel pyrazolines were screened for in vitro antitubercular activity by almar blue dye method against M. tuberculosis H37Rv. All the compounds exhibited excellent activity that could be due to the presence of 3,4-methylenedioxybenzene frame work in the molecules. Some of the compounds also showed in vitro cytotoxicity on EAC cell lines in tryphan blue exclusion assay suggesting their safety.     

HPLC测定金鸡菊中金鸡菊查尔酮含量

目的建立高效液相色谱法测定金鸡菊中金鸡菊查尔酮含量的方法。方法采用Inertsil ODS-3 C18柱（4.6 mm×250 mm,5μm）,以乙腈-1%冰醋酸（80∶20）为流动相,流速1.0 mL/min,检测波长378 nm。结果金鸡菊查尔酮在0.4～4.0μg范围内与峰面积呈良好线性关系,回归方程为Y=31 213X-149 303（r=0.999 9）,平均回收率为99.21%,RSD=1.70%（n=5）。结论本方法简便、准确、重复性好,可用于金鸡菊的质量控制。     

云南豆腐柴的化学成分研究

目的 研究产自云南省的豆腐柴的化学成分.方法 将云南豆腐柴地上部分粉碎后用95％的乙醇提取,所得浸膏分别以石油醚和乙酸乙酯萃取,乙酸乙酯部分经硅胶柱和RP-18柱色谱技术进行分离纯化,运用波谱法对所分离的化合物进行结构解析.结果 从云南豆腐柴中分离得到10个化合物,经波谱分析,鉴定为7-羟基-二氢黄酮(1)、松属素(2)、球松素(3)、3-甲氧基-高良姜素(4)、3,7-二甲氧基-高良姜素(5)、槲皮素3-O-β-D-吡喃木糖苷(6)、2’,4’-二羟基-查儿酮(7)、异甘草素(8)、4-甲氧基-异甘草素(9)、豆蔻素(10).结论 化合物1 ～ 10为首次从云南豆腐柴中分离得到.     

4，2’-二羟基查尔酮及其类似物的合成

目的：合成4,2＇-二羟基查尔酮及其类似物。方法：以羟取代苯甲醛和邻羟基苯乙酮为原料、哌啶为催化剂,通过羟醛缩合反应合成4,2＇-二羟基查尔酮及其5个类似物。结果：成功合成出4,2＇-二羟基查尔酮及其5个类似物,并经MS、^1H-NMR、IR分析确证。结论：以哌啶为催化剂,经羟醛缩合制备查尔酮类化合物具有一定的优越性,值得进一步深入研究。     

白木香查尔酮异构酶基因的克隆鉴定与表达分析

查尔酮异构酶(chalcone isomerase,CHI)是黄酮类成分生物合成途径中的关键酶之一,在植物防御反应中发挥重要作用。本研究根据白木香转录组测序结果并结合RT-PCR技术首次从白木香愈伤组织中克隆得到1个CHI基因,命名为AsCHI1。白木香AsCHI1基因的开放阅读框(ORF)长654 bp,编码蛋白含217个氨基酸,其蛋白分子质量为23.11 kDa。AsCHI1蛋白具有查尔酮异构酶保守的活性位点,系统进化树显示AsCHI1蛋白为I型CHI蛋白,与棉花(Gossypium hirsutum)CHI蛋白亲缘关系较近。构建原核表达载体pET28a-AsCHI1并在E.coli BL21(DE3)菌株中成功表达AsCHI1,利用Ni2+亲和色谱纯化得到可溶性AsCHI1重组蛋白。体外酶活性分析证明重组蛋白AsCHI1可以催化柚皮素查尔酮转化为柚皮素。实时荧光定量PCR检测结果表明白木香愈伤组织经盐、甘露醇、低温以及重金属胁迫诱导后,AsCHI1基因的表达量明显上升;植物激素脱落酸、赤霉素和水杨酸均能够诱导愈伤组织中AsCHI1基因表达,说明AsCHI1在白木香自我防御反应中发挥作用。本研究结果为进一步探讨白木香中黄酮类成分的生物合成及其在白木香防御反应中的作用提供参考。     

Recent advances in therapeutic chalcones

Naturally-occurring and synthetic chalcone compounds have shown promising biological activity and safety profiles and have the potential to be developed as, or more properly, serve as lead compounds for, the discovery of antioxidant, anti-inflammatory, anticancer or anti-infective agents. Mechanisms of the diverse activities observed with chalcone compounds are not well-defined. This review highlights recent developments and patent activities of chalcones with various therapeutic properties.