化合物类药性预测方法的研究

目的 介绍化合物类药性预测方法用于指导类药化合物的合成与收集、类药组合化学库的设计以及高通量筛选前化合物的类药性预测。方法 预测化合物类药性的方法 ,包括简单的虚拟筛选方法、已知药物特征方法、分子水溶性方法、遗传算法和神经网络算法、口服生物利用度预测方法以及血脑屏障通透性预测方法等。结果 化合物类药性预测方法的应用 ,可以大大提高药物发现的机率。结论 在药物发现的早期 ,这些方法对于提高筛选样品的质量 ,减少人力、物力和财力的消耗 ,缩短药物发现的周期 ,将具有一定的指导意义。

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.

Synthesis and Antifungal Activity of 1-(1H-1,2,4-Triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols

Eleven 1-(1H-1,2,4-triazole)-2-(2,4-diflurophenyl)-3-(N-methyl-N-substituted benzylamino)-2-propanols were designed and synthesized, on the basis of the crystal structure of P450 cytochrome 14α-sterol demethylase(CYP51) and the docking results of inhibitors to the active site of the enzyme. All title compounds were first by reported. Results of preliminary biological tests showed that most of title compounds exhibited activity against the seven common pathogenic fungi. Compound 11 showed best antifungal activity with broad antifungal spectrum and proved to be more active against Cryptococcus neoformans, Candida albicans, Microsporum lanosum and Trichophyton rubrum than ketoconazole. Compounds 3, 10 and 4 also had high activities.

Determination of anthraquinone prodrug and its hydrolytically active compounds using RP-HPLC

In order to study the hydrolytic characterization of an anti-inflammatory prodrug （ RI-1 ） in vitro, an effective, accurate and reliable method for the simultaneous determination of the prodrug and its two hydrolytic active compounds is developed using reverse phase high-performance liquid chromatography （RP-HPLC）. The chromatographic separation is performed on an ODS-2 C18 column （250 mm × 4. 6 mm, 5.0 μm particle size） with a simple elution program. The mobile phase is V（ methanol） ： V（0. 1% phosphoric acid solution） =90：10 （adjust pH to 2. 3）. A wavelength of 225 nm and a mobile phase flow rate of 1.0 mL/min are utilized for the quantitative analysis. Excellent linear behaviors over the investigated concentration ranges are observed with values of R2 higher than 0. 999 for all the analytes. The validated method is successfully applied to the simultaneous determination of the prodrug and its active components can be used to detect hydrolytic characterization in vitro.

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.

A Review of Triterpenoids and Their Pharmacological Activities from Genus Kadsura

Plants in genus Kadsura,belong to the Schisandraceae family including genus Schisandra and genus Kadsura,revealed folk efficacy and medicinal application in the treatment of rheumatoid arthritis and gastroenteric disorders for a long history.Previous study indicated that plants from genus Kadsura mainly contain lignans,triterpenoids and essential oils,and showed the active compounds were lignans and triterpenoids.Among all compounds from Schisandraceae family,the triterpenoids between the genus Schisandra and genus Kadsura had obvious differences.In this paper,we reviewed214triterpenoids and their pharmacological activities reported from genus Kadsura in the past30years(from1987to2017),aiming to provide reference for further study.

Carbon quantum dot preparation and application to detecting active ingredients in traditional Chinese medicine

Carbon quantum dots(CQDs)are fluorescent carbon nanomaterials that have been applied to biology,medicine,and optoelectronics,owing to their significant advantages such as simple synthesis methods,low cost,and widely available sources of raw synthesis materials.This review summarizes CQD preparation methods,which include hydrothermal and microwave-assisted synthesis methods,as well as separation methods such as centrifugation,dialysis,and filtration.Additionally,we review the application of CQDs in the detection of active ingredients,primarily phenolic compounds,in traditional Chinese medicine.We also discuss the quenching mechanism of CQD fluorescence using the active ingredients of traditional Chinese medicine.Limitations such as insufficient test selectivity,weak fluorescence intensity,and an unclear quantitative relationship between preparation methods and properties should be resolved for the efficient use of CQDs to detect active ingredients in Chinese medicine.

Study on the Synthesis of 3,4,5-Trimethoxytoluene

The 3,4,5 trimethoxytoluene(TMT) was systhesized using p cresol by three steps including bromination, methoxylation, and methylation with an overall yield of 84%. The structure of TMT was identified by NMR, GC/MS and IR.“One pot”method was used in methoxylation and methylation for economical and convenient consideration. The mechanism for the methoxylation of 2,6 dibromo 4 methylphenol was discussed.

Maqui Aristotelia chilensis （Mol.） Stuntz]-the Amazing Chilean Tree： A Review

A. chilensis （Elaeocarpaceae） is commonly known as maqui, a species widely distributed in Chile. The plant participates in the structure of the Chilean temperate rainforest, currently being found mainly as fragmented forest. Maqui has been listed as the plant with the highest content of phenols when compared with other berries. Multiplication by both, seeds and vegetative has been obtained, opening the possibility to cultivate the plant. Leaves ofmaqui have been traditionally used in the native herbal medicine to treat diverse ailments. Studies indicate the presence of indolic alkaloids, flavonoids, cyaniding glucosides, delfidine, malvidine, petunidine, cumarines and triterpenes. Recent studies support therapeutic properties of maqui leaves, concluding that extracts obtained with polar solvents showed stabilizing capacity of free radicals and antioxidant capacity of plasma in humans. Other works show that fruits could be useful as antioxidant and cardioprotective source. The high contents of anthocyanins and polyglycosylated derivatives make berries of maqui an interesting p｜ant for food and pharmaceutical uses. A. chilensis polyphenols molecular mechanism of action and toxicity can be attributed to functional perturbation of cell membrane lipid bilayers. This review summarizes the research up to date, from propagation methods to chemical properties, indicating weak and lacking aspects.

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.

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.

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.

Comparative pharmacophore modeling of human adenosine receptor A1 and A3 antagonists

Adenosine receptors are promising therapeutic targets in drug discovery. In this study, three-dimensional pharmacophore mod- els of human adenosine receptor A1 and A3 antagonists were developed based on 26 and 23 diverse compounds, respectively. The best A1 pharmacophore model （A1-Hopyl） consists of four features： one hydrogen bond donor, one hydrophobic point and two ring aromatics, while the best A3 pharmacophore model （A3_Hopyl） also has four features： one hydrogen bond ac- ceptor, one hydrophobic point and two ring aromatics. The correlation coefficients were 0.840 for A1 test set with 146 diverse compounds and 0.827 for A3 test set with 238 diverse compounds. In the simulated virtual screening experiments, high en- richment factors of 6.51 and 6.90 were obtained for A1_Hopyl and A3_Hopyl models, respectively. Moreover, two models also showed high subtype-selectivity in the simulated virtual screening experiments. These results could be helpful for the dis- covery of novel potent and selective A1 and A3 antagonists.