新型苯并噁唑(噻唑)衍生物的合成与表征

通过N-氯乙酰或N、N＇-二氯乙酰取代的含氮杂环中间体，4，5-二氯-2-苯基-3-哒嗪酮分别与2-巯基苯并噁唑和2-巯基苯并噻唑反应，合成了8个未见文献报道的苯并噁唑和苯并噻唑衍生物，其结构经^1H NMR，IR，MS及元素分析确认。     

2-取代苯并噁唑衍生物的合成及生物活性

疏基苯并噁唑;2-取代苯并噁唑衍生物的合成及生物活性     

含苯并噁唑基的硫桥杯[4]芳烃衍生物的合成及结构

在碳酸钾存在下, 对叔丁基硫桥杯[4]芳烃(1)分别与端基二溴代烷和碘甲烷反应, 生成硫桥杯[4]芳烃衍生物2～4. 含端基溴代的硫桥杯[4]芳烃衍生物2和4分别与2-巯基苯并噁唑在碳酸钾存在下反应, 生成硫桥杯[4]芳烃衍生物5a～5d. 通过1H NMR, 13C NMR, IR, MS和元素分析等手段对产物进行了表征. 同时, X射线分析确定了硫桥杯[4]芳烃5b的晶体结构.     

Virtual Screening,Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors

Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a–5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber’s guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC₅₀ values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.     

Synthesis and Anticancer Evaluation of Amide Derivatives of 1,3,4-Oxadiazole Linked with Benzoxazole

Russian Journal of General Chemistry - A novel series of amide 1,3,4-oxadiazole linked benzoxazole derivatives 12a–12j are synthesized and their anticancer activity is screened against four...     

Synthesis and Evaluation of Chalcone Derivatives as Novel Sunscreen Agent

Ultraviolet (UV) irradiation is a serious problem for skin health thus the interest in the research to develop sunscreen agent has been increasing. Chalcone is a promising compound to be developed as its chromophore absorbs in the UV region. Therefore, in the present work, we synthesized eight chalcone derivatives through Claisen–Schmidt condensation at room temperature. The evaluation of the optical properties of each chalcone derivatives in the UV region was conducted through spectroscopic and computational studies. The synthesized chalcones were obtained in good yields and they were active in the UV region. The results revealed that more methoxy substituents to chalcone leads toward red shift. All chalcone derivatives have high molar absorptivity value (21,000–56,000) demonstrating that they have the potential to be used as the sunscreen agent. The cytotoxicity assay showed that chalcone derivatives were demonstrating low toxicity toward normal human fibroblast cell, which is remarkable. Therefore, we concluded that the synthesized chalcones in this work were potential to be developed as novel sunscreen agents in real application.     

Epothilone B and its Derivatives as Novel Antitumor Drugs: Total and Partial Synthesis and Biological Evaluation

Summary.  Microtubule stabilizing natural products, as exemplified by paclitaxel (taxol^?), are being considered as novel drugs against malignant therapy resistent solid tumors. Among these compounds, epothilone B and some of its derivatives have emerged as particularly promising candidates for industrial development. The total and partial syntheses of these compounds are described in detail, and some of the most important recent results on their biological activity are discussed. Received December 3, 1999. Accepted December 6, 1999     

Synthesis and Biological Evaluation of Amino Chalcone Derivatives as Antiproliferative Agents

Chalcone is a common scaffold found in many biologically active compounds. The chalcone scaffold was also frequently utilized to design novel anticancer agents with potent biological efficacy. Aiming to continue the research of effective chalcone derivatives to treat cancers with potent anticancer activity, fourteen amino chalcone derivatives were designed and synthesized. The antiproliferative activity of amino chalcone derivatives was studied in vitro and 5-Fu as a control group. Some of the compounds showed moderate to good activity against three human cancer cells (MGC-803, HCT-116 and MCF-7 cells) and compound 13e displayed the best antiproliferative activity against MGC-803 cells, HCT-116 cells and MCF-7 cells with IC₅₀ values of 1.52 μM (MGC-803), 1.83 μM (HCT-116) and 2.54 μM (MCF-7), respectively which was more potent than the positive control (5-Fu). Further mechanism studies were explored. The results of cell colony formatting assay suggested compound 10e inhibited the colony formation of MGC-803 cells. DAPI fluorescent staining and flow cytometry assay showed compound 13e induced MGC-803 cells apoptosis. Western blotting experiment indicated compound 13e induced cell apoptosis via the extrinsic/intrinsic apoptosis pathway in MGC-803 cells. Therefore, compound 13e might be a valuable lead compound as antiproliferative agents and amino chalcone derivatives worth further effort to improve amino chalcone derivatives’ potency.     

吴茱萸碱的合成及其结构表征和体内抗肿瘤作用

以色胺和N-甲基靛红酸酐作为起始原料合成了吴茱萸碱;利用元素分析仪、红外光谱仪、核磁共振谱仪、质谱仪等对合成产物进行了结构表征,并研究了其对小鼠移植性肉瘤S180和小鼠肝癌H22的体内抗肿瘤作用.结果表明,所合成的吴茱萸碱在高、中、低剂量(20 mg·kg-1、10 mg·kg-1、5 mg·kg-1)下均对S180和...     

Research Progress in the Field of Gambogic Acid and Its Derivatives as Antineoplastic Drugs

Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA derivatives have been designed and prepared to improve its shortcomings, such as poor water solubility, low bioavailability, poor stability, and adverse drug effects. So far, GA has been utilized to develop a variety of active derivatives with improved water solubility and bioavailability through structural modification. This article summarized the progress in pharmaceutical chemistry of GA derivatives to provide a reference and basis for further study on structural modifications of GA and expansion of its clinical applications.     

Synthesis and Biological Activity of Some Novel O-Phosphorylated Benzoxazole Derivatives

The phosphorylation of 2-(2′-hydroxyphenyl) benzoxazole has been accomplished with phosphorus oxychloride in a 1:1, 2:1, and 3:1 molar ratio in the presence of a base to yield O-phosphorylated benzoxazole derivatives. Their structures were confirmed by elemental analyses and IR, ¹H NMR, and ³¹P NMR spectral studies. These compounds have been screened for their insecticidal activity against Periplenata americana and were found to be quite active in this respect.     

In Vitro Anti-Candida Activity and Action Mode of Benzoxazole Derivatives

A newly synthetized series of N-phenacyl derivatives of 2-mercaptobenzoxazole, including analogues of 5-bromo- and 5,7-dibromobenzoxazole, were screened against Candida strains and the action mechanism was evaluated. 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanone (5d), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichloro-phenyl)ethanone (5i), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,4,6-trichlorophenyl)ethanone (5k) and 2-[(5-bromo-1,3-benzoxazol-2-yl)sulfanyl]-1-phenylethanone (6a) showed anti-C. albicans SC5314 activity, where 5d displayed MIC_T = 16 µg/mL (%R = 100) and a weak anti-proliferative activity against the clinical strains: C. albicans resistant to azoles (Itr and Flu) and C. glabrata. Derivatives 5k and 6a displayed MIC_P = 16 µg/mL and %R = 64.2 ± 10.6, %R = 88.0 ± 9.7, respectively, against the C. albicans isolate. Derivative 5i was the most active against C. glabrata (%R = 53.0 ± 3.5 at 16 µg/mL). Benzoxazoles displayed no MIC against C. glabrata. Benzoxazoles showed a pleiotropic action mode: (1) the total sterols content was perturbed; (2) 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(3,4-dichlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichlorophenyl)ethanol (8h–i) at the lowest fungistatic conc. inhibited the efflux of the Rho123 tracker during the membrane transport process; (3) mitochondrial respiration was affected/inhibited by the benzoxazoles: 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-chlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanol 8c–d and 8i. Benzoxazoles showed comparable activity to commercially available azoles due to (1) the interaction with exogenous ergosterol, (2) endogenous ergosterol synthesis blocking as well as (3) membrane permeabilizing properties typical of AmB. Benzoxazoles display a broad spectrum of anti-Candida activity and action mode towards the membrane without cross-resistance with AmB; furthermore, they are safe to mammals.     

绿卡色林衍生物的合成、体外代谢及体内活性研究

将选择性5-HT2C受体激动剂类减肥药绿卡色林分子中的仲胺转化成氨基甲酸酯类前药,设计合成了13个氨基甲酸酯类化合物.新化合物的结构经核磁共振波谱、红外光谱及高分辨质谱确证.通过体外代谢稳定性实验,筛选出半衰期长且可通过代谢持续产生绿卡色林的新化合物6b.对化合物6b的大鼠减肥药理实验结果表明,在日剂量相同的条件下,化合物6b给药1次/d比绿卡色林给药2次/d的减肥效果略好.     

Synthesis of Novel Benzisothiazolone Derivatives as Potential Antifoulants

Novel antifoulant 2‐(3‐oxobenzo[d]isothiazol‐2(3H)‐yl)acetohydrazide (2) and 3‐oxobenzo[d]isothiazol‐2(3H)‐yl acetic acid [1‐phenylmethylidene]‐hydrazides (3a–3h) were synthesized in good yields, and their structures were characterized by means of UV, IR, ¹H NMR, MS, and elemental analysis.     

The Synthesis and Herbicidal Evaluation of Fluorine-Containing Phenoxyacetoxyalkylphosphonate Derivatives

To investigate the influence of a fluorine moiety on the biological activity of phenoxyacetoxyalkylphosphonates, a series of fluorine-containing phenoxyacetoxyalkylphosphonates were synthesized and screened for herbicidal activity in a greenhouse. The majority of the title compounds showed better preemergence activity than postemergence activity against the test plants, especially on monocotyledon. Compound 5l exhibited notable activity. Results showed that by introducing a fluorine moiety to the parent structure of phenoxyacetoxyalkylphosphonates, a series of new compounds with satisfactory herbicidal activity could be synthesized. A reasonable combination of a fluorine moiety and other substituents on the benzene ring had a great influence on the herbicidal activity.     

藤黄酸氰基衍生物的合成及抗肿瘤活性

以藤黄酸为原料,经过酯化反应或酰胺化反应,在C-30位的羧基上引入不同的烷氰基或芳香氰基,设计合成了7个藤黄酸氰基衍生物,其中6个为新化合物,其结构经MS和¹H NMR确证。 采用四氮唑蓝(MTT)法测试了合成化合物对肝癌细胞(HepG2)、结肠腺癌细胞(RKO)和卵巢腺癌细胞(OVCAR-3)的体外抗肿瘤活性,结果表明,所合成的化合物均具有一定的抗肿瘤活性,其中化合物4和6的抗肿瘤活性明显优于阳性对照物藤黄酸。     

Glycogen as a Biodegradable Construction Nanomaterial for in vivo Use

It is demonstrated that glycogen as a biodegradable and inexpensive material coming from renewable resources can be used as a carrier for the construction of in vivo imaging nanoagents. The model system considered is composed of glycogen modified with gadolinium and fluorescent labels. Systematic studies of properties of these nanocarriers by a variety of physical methods and results of in vivo tests of biodegradability are reported. This represents, to the authors' best knowledge, the first such use of glycogen.

     

Epothilone B and its Derivatives as Novel Antitumor Drugs: Total and Partial Synthesis and Biological Evaluation

 Microtubule stabilizing natural products, as exemplified by paclitaxel (taxol^?), are being considered as novel drugs against malignant therapy resistent solid tumors. Among these compounds, epothilone B and some of its derivatives have emerged as particularly promising candidates for industrial development. The total and partial syntheses of these compounds are described in detail, and some of the most important recent results on their biological activity are discussed.     

Design,Synthesis and Biological Activity of C3 Hemisynthetic Triterpenic Esters as Novel Antitrypanosomal Hits

Research for innovative drugs is crucial to contribute to parasitic infections control and eradication. Inspired by natural antiprotozoal triterpenes, a library of 12 hemisynthetic 3-O-arylalkyl esters was derived from ursolic and oleanolic acids through one-step synthesis. Compounds were tested on Trypanosoma, Leishmania and the WI38 cell line alongside with a set of triterpenic acids. Results showed that the triterpenic C3 esterification keeps the antitrypanosomal activity (IC₅₀≈1.6–5.5 μm ) while reducing the cytotoxicity compared to parent acids. Unsaturation of the ester alkyl chain leads to an activity loss interestingly kept when a sterically hindered group replaces the double bond or shields the ester group. An ursane/oleanane C3 hydroxylation was the only important feature for antileishmanial activity. Two candidates, dihydrocinnamoyl and 2-fluorophenylpropionyl ursolic acids, were tested on an acute mouse model of African trypanosomiasis with significant parasitemia reduction at day 5 post-infection for the dihydrocinnamoyl derivative. Further evaluation on other alkyl/protective groups should be investigated both in vitro and in vivo.