环境激素类有机污染物的微生物降解和药物类化合物的残留问题(英文)

合成有机物在环境中的残留和危害已不仅仅局限于其毒性、富集、致畸和致突变,同时还能干扰包括人类在内的生物的内分泌调节作用。近年来发达国家已开始逐渐有了环境方面的条例,限制和控制这类化合物在水及食物链中的含量。现已清楚地知道,部分除草剂和杀虫剂(如阿特拉津、DDT),塑料的添加增塑剂均有内分泌激素活性,从而对生物的正常生长发育造成不良的影响。而这些化合物不但广泛存在于环境中,在特定的环境中其含量更是非常之高。以增塑剂邻苯二甲酸和邻苯二甲酸二甲酯为例,它们在填埋渗出液中的含量可高达10g·L^(-1)。在我们研究这类化合物的微生物降解时发现,从活性污泥和红树林中富集到的好氧微生物能将这类化合物完全矿化,且反应速度很快。同时也发现,在降解邻苯二甲酸二甲酯时,单一的纯菌不能完全降解这类化合物,而二种或三种组合的纯菌可以在一周内将500mg·L^(-1)的底物完全矿化。我们已分离、鉴定出中间产物,建立起了降解途径。研究的结果证实,邻苯二甲酸二甲酯类环境激素是能够在排放前通过微生物的作用达到完全矿化的。另一方面,药物类化合物的残留问题也是一个逐渐显现出的环境问题,这方面的研究应引起更多的关注和重视。

Three Anthraquinones Isolated from Aster tataricus L.f

The roots and rhizomes of Aster tataricus L. f (Zi-wan) is a traditionalChinese medicine, which has been used for relieving cough and resolving phlegm. Previousinvestigation of the species resulted in the isolation and identification of triterpenes,triterpenoid saponins, cyclic pentapeptides, and oligopeptides. We have also reported thepolyphenols and a dipeptide isolated from the species. In this paper, the isolation and structureelucidation of three anthraquinones, chrysophanol (1), physciori (2), and emodin (3), are described.Chrysophanol and physcion were isolated from family Composi-tae for the first time.

Chemical constituents of marine medicinal mangrove plant Sonneratia caseolaris

Twenty-four compounds including eight steroids （1-8）, nine triterpenoids （9-16, 24）, three flavonoids （20-22）, and four benzenecarboxylic derivatives （17-19, 23） were isolated and identified from stems and twigs of medicinal mangrove plant Sonneratia caseolaris. The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data. Among these rnetabolites, compounds 1, 4-20 and 22-24 were isolated and identified for the first time from S. caseolaris. In the in vitro cytotoxic assay against SMMC-7721 human hepatoma cells, compound 21 （3＇,4＇,5,7-tetrahydroxyflavone） exhibited significant activity with IC50 2.8 μg/mL, while oleanolic acid （14）, 3,3＇-di-O-methyl ether ellagic acid （18）, and 3,3＇,4-O-tri-O-methyl ether ellagic acid （19） showed weak activity. None of these compounds displayed significant antibacterial activites.

Computational Evaluation of Selectivity of Triazole-and Amide-Based Drug Candidates, Flavanone Derivatives and Synthesized Steroid Compounds for Treatment of Diabetes Type II

Inhibition of 11βHSD1 （11-beta-hydroxysteroid dehydrogenase 1） is a promising strategy in drug treatment of diabetes. Several 11βHSDI inhibitors have been proposed; however, their selectivity to 11βHSD1 over its isozyme 11βHSD2 （11-beta-hydroxysteroid dehydrogenase 2） has not been fully reported. The authors sought to provide a short list of top potent and selective compounds along with their detailed binding modes and pharmacophore models, Molecular docking was used for initial screening of a set of 23 potent inhibitors reported by previous experimental studies. After that, selected promising entries were reassessed by molecular dynamics simulations, followed by hydrogen bond analysis. Pharmacophore models of all drug candidates and binding modes of some selected drugs were analyzed. Among the 23 compounds, only four inhibitors were identified as potent and selective drug candidates. Binding energies, 3D pharmacophores and binding modes of the four compounds with 11βHSDI are also discussed in detail in this study.

Sulfuryl Group-Involved Drugs Approved by the Food and Drug Administration(FDA)from 2021 to 2023

Organic sulfone compounds,exhibiting interesting bioactivities,were widely applied in the field of pharmaceutical and medicine.And numerous of sulfuryl group-involved drugs were approved by the Food and Drug Administration(FDA).Odevixibat,maralixibat chloride and belzutifan approved in 2021 could be applied in the treatment of progressive familial intrahepatic cholestasis(PFIC),cholestatic pruritus and clear cell renal cell carcinoma(ccRCC),respectively.In 2022,abrocitinib,pyrukynd and voquezna were approved for the treatment of atopic dermatitis,pyruvate kinase deficiency(PKD)and acid-related disorders,respectively.Defencath for preventing bloodstream infections,sparsentan for treatment of proteinuria related to IgA nephropathy,and xacduro for treatment of hospital-acquired bacterial pneumonia(HABP)were approved in 2023.In this review,the synthesis and therapies of these sulfuryl group-involved drugs approved from 2021 to 2023 are discussed in details.

Limitations of the use of MTT assay for screening in drug discovery

The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay is a routine cell viability assay for cell proliferation and cytotoxicity, which is widely used in many fields, especially in screening for drug discovery. However, this assay exhibits limitations in the presence of particular compounds and under certain assay conditions, which may yield false screening results. For example, polyphenols that are extracted from natural sources can react with MTT in the absence of living cells and thus interfere with the screening results. We measured the absorbance of 15 polyphenols extracted from green tea and showed that the phenolic hydroxyl groups in the polyphenols are responsible for the reduction of MTT to formazan. When three or more phenolic hydroxyl groups were present on a conjugated polyphenol, a significantly increased MTT reduction was observed. Moreover, the type of medium also had an effect on the absorbance value, in the following order： ct-MEM ＋ 10% FBS〉 a-MEM〉DMEM/F12〉PBS. The absorbance of the MTT assay recorded at 570 nm is more sensitive than that measured at 595 nm. These results will improve the cell-based assay of polyphenols and clarify the limitations of the MTT assay as a method of screening in drug discovery.

Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants

Scutellaria baicalensis Georgi, or Chinese skullcap, has been widely used as a medicinal plant in China for thousands of years, where the preparation from its roots is called Huang-Qin. It has been applied in the treatment of diarrhea, dysentery, hypertension, hemorrhaging, insomnia,inflammation and respiratory infections. Flavones such as baicalin, wogonoside and their aglycones baicalein wogonin are the major bioactive compounds extracted from the root of S. baicalensis. These flavones have been reported to have various pharmacological functions, including anti-cancer,hepatoprotection, antibacterial and antiviral, antioxidant,anticonvulsant and neuroprotective effects. In this review,we focus on clinical applications and the pharmacological properties of the medicinal plant and the flavones extracted from it. We also describe biotechnological and metabolic methods that have been used to elucidate the biosynthetic pathways of the bioactive compounds in Scutellaria.

Relationship between Temperaments of Medicinal Plants and Their Major Chemical Compounds

Objective: To determine any relationship between temperaments of medicinal plants referred to traditional Iranian manuscripts and their major chemical compounds. Methods: Plants used in traditional Iranian medicine were categorized based on their major chemical compounds including alkaloids, phenolic compounds, and essential oils. Their temperaments were extracted from traditional herbal pharmacopeias of Iran. The possible relationship between major chemical compounds and temperaments of each group were evaluated. Results: Plants containing phenolic compounds as their major constituents are hot and dry temperaments except those contain tannins with cold and dry temperaments. Plants containing essential oils have hot and dry temperaments except those whose major essential oils with alcoholic structure which have cold and dry temperaments. Alkaloid-containing plants have cold and dry or hot and dry temperaments based on their alkaloidal structures. Conclusions: There is a close relationship between major chemical compounds of medicinal plants and their temperaments mentioned in traditional Iranian manuscripts.