Synthesis,in‐vitro Microbial and Cytotoxic Studies of New Benzimidazole Derivatives

Several new classes of benzimidazole derivatives were synthesized and evaluated for in‐vitro antimicrobial and cytotoxic activities. The results showed that all synthesized compounds exhibited moderate antimicrobial activity, and compounds 2 , 4 , and 13 displayed cytotoxic activity (as LD₅₀) at the concentration 1×10^–3 M against Artemia salina.     

Green synthesis and antimicrobial evaluation of some new trifluoromethyl-substituted hexahydropyrimidines by grinding

A series of trifluoromethyl-substituted hexahydropyrimidine derivatives were efficiently synthesized in excellent yields via one-pot three-component reaction of aromatic aldehydes, ethyl trifluoroacetoacetate and thiourea(urea) in presence of p-toluenesulfonic acid under solvent-free conditions at room temperature by grinding. The present method does not involve any hazardous organic solvent and has proven to be simple, efficient, environmentally benign and cost-effective compared with the classical synthetic methods.These compounds were screened for their antibacterial activities against Escherichiacoli and Bacillus thuringiensis and found to exhibit remarkably better antibacterial activities than the control drug.     

Synthesis and antimicrobial activities of novel quinoline derivatives carrying 1,2,4-triazole moiety

A new class of quinoline derivatives containing 1,2,4-triazole moiety were synthesized from derivatives of 4-hydroxy-8-(trifluoromethyl)quinoline-3-carbohydrazide 4 through multi-step reactions. The compound 4, on treatment with substituted Isothiocyanates yielded quinoline-thiosemicarbazides 5a–c, which were conveniently cyclized to (5-mercapto-4H-triazol-3-yl)-quinolin-4-ols 6a–c in basic medium. These intermediates were then transformed to their respective chloro derivatives 7a–c by treatment with phosphorus oxychloride, which on further reaction with different biologically active rare amines yielded the target compounds 8a–g, 9a–h and 10a–h in good yield. The ultimate step, involving nucleophilic substitution reaction was achieved by microwave-induced technique, which has reduced the reaction time drastically as well as improved the yield when compared to conventional heating. The newly synthesized final compounds were evaluated for their in vitro antibacterial and antifungal activities against four strains each. Preliminary results indicated that most of the compounds demonstrated very good antimicrobial activity, comparable to the first line standard drugs. The most effective compounds have exhibited activity at MIC of 6.25 μg/mL.     

Anticancer Activity of Indeno[1,2-b]-Pyridinol Derivative as a New DNA Minor Groove Binding Catalytic Inhibitor of Topoisomerase IIα

Topoisomerase IIα has been a representative anti-cancer target for decades thanks to its functional necessity in highly proliferative cancer cells. As type of topoisomerase IIα targeting drugs, topoisomerase II poisons are frequently in clinical usage. However, topoisomerase II poisons result in crucial consequences resulted from mechanistically induced DNA toxicity. For this reason, it is needed to develop catalytic inhibitors of topoisomerase IIα through the alternative mechanism of enzymatic regulation. As a catalytic inhibitor of topoisomerase IIα, AK-I-191 was previously reported for its enzyme inhibitory activity. In this study, we clarified the mechanism of AK-I-191 and conducted various types of spectroscopic and biological evaluations for deeper understanding of its mechanism of action. Conclusively, AK-I-191 represented potent topoisomerase IIα inhibitory activity through binding to minor groove of DNA double helix and showed synergistic effects with tamoxifen in antiproliferative activity.     

三氟甲基氨酚喹类似物的合成及其抗疟活性

本文报道了22个7-三氟甲基和2-甲基-7-三氟甲基氨酚喹类似物的合成。用伯氏疟原虫(plasmodium berghei)ANKA正常株感染小鼠作抑制性治疗试验,在剂量为(10 mg/kg)/d×4和(20 mg/kg)/d×4时,有11个化合物(Ⅰ_1～9,Ⅱ₃和Ⅱ₆)对疟原虫完全抑制。其中3个化合物(Ⅰ₂,Ⅰ₆和Ⅰ₇)在剂量为(5 mg/kg)/d×4时,就能对原虫完全抑制。12个化合物(Ⅰ_1～10,Ⅱ₃和Ⅱ₆)用伯氏疟原虫ANKA抗氯喹株感染小鼠作治疗试验,剂量为(20 mg/kg)/d×4,2个化合物(Ⅰ₄和Ⅱ₃)在受试的5只小鼠中,原虫完全被抑制的鼠分别为3和4只,用相同剂量的对照药物盐酸氨酚喹治疗,原虫仍为阳性。     

一些对-、邻-和间-三氟甲基桂皮酰胺的合成及其抗惊活性

合成了p-,o-和m-三氟甲基取代桂皮酰胺化合物,用核磁共振谱和红外光谱确定了它们为反式构型。抗惊活性试验结果表明:p-和m-三氟甲基导致比较高的抗惊活性。p-三氟甲基的Hammett常数高于m-三氟甲基,原期望p-三氟甲基桂皮酰胺的活性高于m-三氟甲基化合物,但两者的抗惊活性无明显差别。紫外光谱证明o-三氟甲基的空间效应影响苯环和烯烃的共扼,从而使化合物的抗惊活性明显下降。     

Inhibitory action of a new proton pump inhibitor, trifluoromethyl ketone derivative, against the motility of clarithromycin-susceptible and-resistant Helicobacter pylori

We previously reported that a trifluoromethyl ketone derivative, 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18), exhibited the potent antibacterial activity against Helicobacter pylori, but had no urease activity. In order to clarify the mechanism of anti-H. pylori action of TF18, we evaluated the growth and motility of TF18 on clarithromycin-susceptible H. pylori (CSHP) and -resistant H. pylori (CRHP). An effective proton pump inhibitor (TF18) had remarkable dose-dependent antibacterial activity and was able to inhibit the flagellar motor of both CSHP and CRHP isolates. The antimotility effect of TF18 was more pronounced at subinhibitory concentration in CRHP than in CSHP. The swimming (the forward motion) was more sensitive to the inhibition than the tumbling. Based on the results, it is supposed that TF18 works as an uncoupler similar to the ‘clutch’ in a biological motor, in which counterclockwise rotation is more sensitive to the effect of TF18 than the clockwise rotation.     

次氟酸三氟甲酯致大鼠骨损害的初步病理观察

本文报告大鼠吸入有机氟化物——次氟酸二氯甲酯后,骨骼的病理改变及骨氟含量之间的关系。健康Wistar大鼠24只,随机分成3组,分别用0、0.067和0.1ppm的次氟酸三氟甲酯在1m~3有机玻璃染毒柜中静式吸入染毒,每日2h,每周5d,共23周。结果显示:实验组大鼠髂骨氟含量明显高于对照组(P<0.05);组织病理学检查发现:次氟酸三氟甲酯有成骨效应,而且病变主要集中在0.1ppm组大鼠髂骨,特别是骨外膜和哈佛氏骨管内,其病变特点为骨外膜活跃性局灶性成骨细胞反应以及骨或骨样组织形成。