6-连氮和6α-甲氧基-6β-取代腙青霉素的合成及抗菌活性

本文报道新颖的6-连氮和6α-甲氧基-6β-取代腙青霉素的合成及引入6α-甲氧基的新方法。这类化合物对一些阴性菌和阳性菌有中等活力,且引入6α-甲氧基之后对细菌的抑制作用增强。     

11α-羟基炔雌醚和11α-甲氧基炔雌醚的合成及其抗生育作用

为了寻找抗生育药物,从△⁹⁽¹¹⁾-雌素酮开始,经环戊醚化、缩酮化、硼氢化-氧化、甲基化、脱缩酮、乙炔化等反应合成了11α-羟基炔雌醚、11α-甲氧基炔雌醚。目的化合物及相应中间体的结构依据波谱分析等确定。小鼠实验表明这两个化合物不具明显抗生育活性。     

β-锗代-α-氨基酸衍生物的合成及抗肿瘤活性

自六十年代初期发现羧乙基锗倍半氧化物(Ge—132)广泛的生物活性以来,已有许多相应的有机锗化合物被发现,在抗肿瘤活性方面,因有毒性较低、抗瘤谱广等一系列优点而引起人们广泛的兴趣,但由于活性较低影响了应用及发展,据文献报道,有机锗倍半氧     

血吸虫病化学治疗的研究——Ⅳ.β-(5-硝基-2-呋喃)丙酰胺类及其α,β-二溴取代衍生物的合成

本文报道38个β-(5-硝基-2-呋喃)丙酰胺及其α,β-二溴取代衍生物的合成。这类化合物的制备是以相应的β-(5-硝基-2-呋喃)丙烯酰胺类化合物(Ⅰ)进行催化氢化或与溴加成而得。经动物筛选发现β-(5-硝基-2-呋喃)丙烯酰胺类的丙烯双键以氢饱和以后生成丙酰胺类化合物(Ⅱ),对感染日本血吸虫病的小白鼠完全失去治疗或预防作用。而以溴饱和双键的α,β-二溴化合物(Ⅲ)则仍然有较显著的杀虫作用。其中尤以β-(5-硝基-2-呋喃)-α,β-二溴丙酰异丙胺(Ⅲ₁₁)和β-(5-硝基-2-呋喃)-α,β-二溴丙酰甘氨酸乙酯(Ⅲ₂₄)最为显著,后者曾试用于临床,证明有一定疗效。     

2β-(4′-甲基- 1′-哌嗪基)- 3α-羟基-16,17-取代-5α-雄甾烷的合成

为了寻找心血管系统药物,以表雄酮为原料,合成了7个16,17位取代的目标化合物:2β-(4’-甲基-1’-哌嗪基)-3α-羟基-5α-雄甾-17-酮、2β-(4’-甲基-1’-哌嗪基)-3α,17β-二羟基-5α-雄甾烷、2β-(4’-甲基-1’-哌嗪基)-3α-羟基-16α-溴-5α-雄甾-17-酮、2β-(4’-甲基-1’-哌嗪基)-3α,16α-二羟基-17-氧-5α-雄甾烷、2β-(4’-甲基-1’-哌嗪基)-3α,16α-二羟基-17-肟-5α-雄甾烷、2β-(4’-甲基-1’-哌嗪基)-3α,16α-二羟基-17β-氨基-5α-雄甾烷和2β—(4’-甲基-1’-哌嗪基)-3α,17β-二羟基-16β-氨基-5α-雄甾烷。初步药理试验结果表明它们都有不同程度的抗心律失常活性。     

酒石酸酯/β-环糊精分离体系分离α-环己基扁桃酸对映体

目的建立α-环己基扁桃酸对映体的萃取拆分方法并考察各个影响因素对拆分效果的影响。方法以D-酒石酸酯和β-环糊精为手性选择体来萃取拆分α-环己基扁桃酸对映体。结果考察了酒石酸酯/β-环糊精分离体系中萃取拆分α-环己基扁桃酸对映体的分配行为，着重研究了酒石酸酯烷基链长度、pH值、D-酒石酸酯浓度和β-环糊精浓度对萃取拆分效果的影响。结论D-酒石酸异丁酯与R对映体形成的复合物稳定性比与S对映体形成的好；随着pH值增大，分配比和分离因子都降低；D-酒石酸酯和β-环糊精浓度对萃取拆分的影响较大。     

β-丁香烯代谢产物和结构改造的研究

从β-丁香烯代谢产物中分离得到一种有药理活性的化合物,经光谱分析及化学反应证明其结构为β-丁香酮(8)。根据代谢产物的化学结构以及构-效关系理论,对β-丁香烯进行了结构改造研究,结果得到一种活性较强的半合成产物,为无定形长丝状物,其结构被鉴定为β-丁香烯醇(3)。药理实验表明化合物(8)及(3)对豚鼠离体气管平滑肌均有较强的松弛作用,化合物(3)还能明显抑制组织胺和乙酰胆碱诱发的豚鼠哮喘,其作用持久而毒性低,可望成为一种新型的平喘药物。     

新型头孢菌素的合成和抑菌试验

从7-氨基头孢烷酸(7 ACA)和7-氨基-3-去乙酰氧基头孢烷酸(7 ADCA)合成了六个7-取代连氮基头孢菌素和六个7α-甲氧基-7β-取代腙基头孢菌素,体外抑菌试验表明大部分化合物的抑菌活性较弱。     

半合成β-1,4-葡聚糖硫酸钠的抗凝血特性

目的研究半合成β-1,4-葡聚糖硫酸钠(Na-MCS)的抗凝血效果和作用机制。方法采用凝固分析法、以肝素为阳性对照进行抗凝血效果的评价，再通过发色底物法对凝血因子进行抑制分析，揭示Na-MCS的抗凝血作用机制。结果0.6 μg·mL^-1 Na-MCS即可显著延长APTT和TT，但在更高浓度下对PT影响仍不大，使正常人血浆的APTT延长1倍的Na-MCS剂量为0.7 μg·mL^-1，低于活性为150 u·mg^-1的肝素。结论在一定浓度范围内，Na-MCS的抗凝血活性与肝素相当，Na-MCS通过抗凝血酶AT-III的调节作用来抑制凝血因子IIa和Xa的活性，从而产生抗凝血作用。     

α-胺基苄基膦酸酯的合成及其生物活性

目的寻找具有内皮依赖性舒张血管活性的新结构胺基膦酸酯类化合物。方法运用一种新型的类Mannich反应，以生物电子等排体原理设计合成了一系列α-胺基苄基膦酸酯类化合物，并运用离体大鼠血管环和离体豚鼠回肠收缩实验观察其舒张血管活性及其对M受体的激动作用。结果共合成了7个新的α-胺基苄基膦酸酯类目标化合物，其结构经IR，¹H NMR和元素分析确定。初步离体血管环实验和离体豚鼠回肠收缩实验结果显示，化合物2a，2b和2c有一定的舒张血管活性且不激活平滑肌M受体。结论在浓度为1×10^-5 mol·L^-1时，化合物2b和2c有较强的舒张血管活性，其舒张率分别为(67±21)%，(82±18)%，而且不激动M受体，其中，化合物2b有内皮依赖性的舒张血管反应。     

国产醋酸甲地孕酮的质量研究:6-羟基-6-甲基-17α-乙酰氧基黄体酮差向异构体的分离与鉴定

用柱层析及薄层层析对国产醋酸甲地孕酮的杂质进行了分析,共分离出7个杂质点:Ⅰ₁,Ⅰ₂,Ⅰ₃,Ⅰ₄,Ⅰ₅,Ⅰ₆,Ⅰ₇,并对其中Ⅰ₃和Ⅰ₄进行分离纯制及光谱分析,确定其结构为6β-羟基-6α-甲基-17α-乙酰氧基黄体酮及其差向异构体6α-羟基-6β-甲基-17α-乙酰氧基黄体酮。本文报道了薄层层析条件(硅胶GF₂₅₄,展开剂:醋酸乙酯-甲苯=7:3)以及光谱鉴别的依据。     

21-氯代达哪唑及其C6-脱氢物的合成

Synthesis was undertaken of 21-chloro-danazol (Ⅳa) and 21-chloro-6-dehydro-danazol (Ⅳb). The binding ability of these compounds to progesterone receptor were examined and were found to be less active than danazol.Compound (Ⅳa) showed significant activity for eary pregnancy termination effect in Sprague-Dawley rats.     

含α,β-不饱和酮的Mannich碱的合成及抑菌活性

合成了12个含α,β-不饱和酮的Mannich碱化合物及1个环状Mannich碱,经元素分析、红外、紫外、核磁及质谱确定其化学结构,并对其抑菌作用进行了研究。     

Synthesis of new 2-thiouracil-5-sulphonamide derivatives with antibacterial and antifungal activity

2-Thiouracil-5-sulphonic acid N-(4-acetylphenyl) Amide (1) was reacted with a series of aromatic aldehydes giving chalcones 2 (Claisen-Schemidt reaction), some of these chalcones were reacted with urea and thiourea giving pyrimidine-2-one and pyrimidine-2 thione derivatives respectively of the type 3a,b and 4a,b. In addition many chalcones were reacted with hydroxylamine hydrochloride giving isoxazoline derivatives 5a,b. They could also reacted with phenylhydrazine to give pyrazoline derivatives 6a,b, chalcones also were reacted withethylcyano acetate and/or malononitryl in pyridine giving pyran derivatives 7a,c and 8a,c. In another pathway chalcones were epoxidised by H2O2 giving epoxides 9a,c which in turn were reacted with phenylhydrazine giving 4-hydroxypyrazoline derivatives 10a,c. In another reaction chalcones were reacted with ethylcyanoacetate in presence of amm.acetate giving pyridone derivatives 11a,d which could be prepared also in exellent yield from compound 1 by its reaction with certain aromatic aldehydes and ethylcyanoacetate in presence of ammonium acetate. Finally, compound 1 was reacted with semicarbazide giving semicarbazone intermediate 12 which in turn was reacted with thionyl chloride giving thiadiazole derivative 13. The biological effects of some of the new synthesized compounds were also investigated.     

Evaluation of Cassia occidentalis for in vitro cytotoxicity against human cancer cell lines and antibacterial activity

Objective:

To evaluate the in vitro cytotoxicity and antibacterial properties of Cassia occidentalis (whole plant) via alcoholic, hydro-alcoholic, and aqueous extracts against eight human cancer cell lines from six different tissues and four bacterial strains.

Material and Methods:

in vitro cytotoxicity against the human cancer cells, cultured for 48h in presence of different concentrations C. occidentalis extracts and percentage of cell viability, was evaluated using the sulforhodamine-B (SRB) assay. The antibacterial activity was performed using the standard protocol against bacterial strains.

Results:

It was observed that aqueous extract of C. occidentalis (whole plant) had more potential than hydro-alcoholic and alcoholic extracts against HCT-15, SW-620, PC-3, MCF-7, SiHa, and OVCAR-5 human cancer cell lines at 100, 30, and 10 μg/ml in a dose-dependent manner. The hydro-alcoholic extract showed potential against Bacillus subtillis.

Conclusion:

The plant can be explored for the possible development of lead molecules for drug discovery.     

11个单环β-内酰胺类化合物的合成及其抗菌活性初探

根据单环β—内酰胺类化合物定量构效关系研究的结果提示，以N-苄基-3(S)-邻苯二甲酰亚胺基-4(S)-[4(S)-2，2-二甲基-1，3二氧环戊-4-基]-2-氧吖丁啶为原料，设计合成了11个新的单环β—内酰胺类化合物，其结构经MS、^1H—NMR或IR所确证，并测定了它们的体外抗菌活性，结果表明，它们均有抗菌作用，但抗菌活性低于对照品。     

Synthesis and antibacterial activity of triphenyltinbenzoate

Triphenyltinbenzoate was synthesized using triphenyltinchloride and silver benzoate prepared from sodium benzoate. The structure of the synthetic compound was elucidated by spectral and C, H analysis. The antibacterial activities of the organotin compound were determined against four bacteria namely Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Streptococcus pyogenes (clinical isolate) and Pseudomonas aeruginosa (ATCC 27853) in vitro experiment. All the bacteria were inhibited at a concentration of 200 μg/ml and 20 μg/ml in dimethylsulphoxide solution and the minimum inhibitory concentration was found to be same, 7.5 μg/ml for Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes and 10 μg/ml for Pseudomonas aeruginosa.     

Synthesis of novel analogues on the α-carbon of houttuyfonate and SAR analysis of antibacterial activity with MOPAC

Three novel α-carbon derivatives of houttuyfonate—HOU-C₈C₁, HOU-C₈C₂, and HOU-C₈C₄—were designed and synthesized, and tested for their in vitro antibacterial activities against seven bacterial strains. A set of molecular properties of houttuyfonate and its five analogues were analyzed by MOPAC. Results indicated that the antibacterial activity of HOU-C₈C₁ is lower than that of HOU-C₈. However, among HOU-C₈C _n (n = 1, 2, 4), as the hydrophobicity increased so did the activity, especially against Gram-positive bacteria. For the isomeric compounds HOU-C₈C₂ and HOU-C₁₀, HOU-C₈C₄, and HOU-C₁₂, the more negative the charges on carbon atom 2, the stronger the antibacterial activity exhibited. This suggests that the C(2) position is the antibacterial active center of houttuyfonate analogues, and that the weak antibacterial activities are possibly caused by the net negative charges on houttuyfonate homologues.     

Synthesis and antibacterial activity of N-[5-chlorobenzylthio-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives

A series ofN-[5-(chlorobenzylthio)-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives (4a-1) have been synthesized by reaction of piperazinyl quinolones with 5-chloro-2-(chloroben-zylthio)-1,3,4-thiadiazoles. Their structures were confirmed by elemental analysis, IR and NMR spectra. The antibacterial activities of4a-1 against a variety of Gram-positive and Gram-negative bacteria were determined. Several compounds showed a good antibacterial activity against Gram-positive bacteria among which, compound 4e with a 2-chlorobenzylthio moiety in ciprofloxacin derivative, exhibited high activities againstStaphylococcus aureus andStaphylococcus epidermidis (MIC=0.06 μg/mL). The structure-activity relationship (SAR) study revealed that the position of chlorine atom on benzyl moiety would dramatically affect the antibacterial activities of the synthesized compounds.