JunceellinA水解产物的制备及其对肺癌A—549细胞的活性

从南海鳞灯芯珊瑚Ｊｕｎｃｅｌｌａｓｑｕａｍａｔａ分离出的ＪｕｎｃｅｅｌｌｉｎＡ（ＪＡ）分界用Ｋ２ＣＯ３和２ｍｏｌ／ＬＨＣｌ水解得到二羟基产物（ＪＡ）和四羟基产物（ＪＡ２），初步药理试验显示，ＪＡ１和ＪＡ２浓度在３０～５０μｇ／ｍＬ，具有抑制肺癌Ａ－５４９细胞生长的活性，ＪＡ２的效应比ＪＡ１强，ＪＡ２对正常人细胞的生长无影响。     

（＋）—布雷菲德菌素A的中间体合成研究Ⅱ.闭环反应及相关环戊…

利用氰基环氧化物（１）分子内的闭环反应，制备具有抗真菌、抗病毒等生物活性的（＋）－布雷菲德菌素Ａ的重要中间体即（１Ｒ，２Ｒ，１Ｒ）－１－（１‘－二甲叔丁硅氧基－２’－羟基乙基）－２－氰基环戊烷（３）的过程及相关环戊烷衍生物的制备。     

（＋）－布雷菲德菌素A的中间体合成研究Ⅱ．闭环反应及相关环戊烷衍生物的制备

利用氰基环氧化物（１）分子内的闭环反应，制备具有抗真菌、抗病毒等生物活性的（＋）－布雷菲德菌素Ａ的重要中间体即（１Ｒ，２Ｒ，１′Ｒ）－１－（１′－二甲叔丁硅氧基－２′－羟基乙基）－２－氰基环戊烷（３）的过程及相关环戊烷衍生物的制备     

多发性肌炎病人血清自身抗体测定

应用间接免疫荧光及免疫印迹技术检测６５例ＰＭ、ＤＭ、ＭＣＴＤ和ＰＭ－Ｓｃｌ，检出ＡＮＡ、ＡＳＡ及７种ＥＮＡ多肽抗体，其阳性率为８６．２％。ＥＮＡ多肽抗体中ＭＣＴＤ抗ＲＮＰ抗体阳性率最高（８７．５％），ＰＭ抗Ｊｏ－１抗体次之（２８．６％），ＤＭ抗Ｊｏ－１抗体阳性率较低（１０％）。抗Ｊｏ－１抗体主要存在于ＰＭ，可出现于疾病早期并盱整个病程。抗Ｊｏ－１抗体滴度与ＣＫ水平和疾病的严重程度有关，病情加重常伴     

高频通气治疗成人呼吸迫综合征12例报告

通过综合治疗１２例成人呼吸窘迫综合征（ＡＲＤＳ）基础上，用高频喷射呼吸机间隙给氧治疗ＡＲＤＳ，旨在了解提高患者动脉血氧分压（ＰａＯ２）的疗效及治疗效果，凡存在ＲＤＳ病因的患者，一旦发现ＡＲＤＳ的早期征象，应立即给予祛除病因及其它综合治疗，同时交替给高频喷射呼吸机（ＨＦＪＶ）通气治疗及一般正常浓度氧疗。治愈率达６７％，死亡率为３３５。ＨＦＪＶ通气治疗与一般浓度氧疗是提高ＡＲＤＳ患者ＰａＯ２较好的方法     

（4R）—2,2—二甲基—1,3—二氧戊环—4—羧酸甲酯的制备

（４Ｒ）┐２，２┐二甲基┐１，３┐二氧戊环┐４┐羧酸甲酯的制备ＰＲＥＰＡＲＡＴＩＯＮＯＦＭＥＴＨＹＬ（４Ｒ）┐２，２┐ＤＩＭＥＴＨＹＬ┐１，３┐ＤＩＯＸＯＬＡＮＥ┐４┐ＣＡＲＢＯＸＹＬＡＴＥ赵军（浙江工业大学化学工程学院，杭州３１００３２）ＺＨＡＯＪ...     

2,6—二甲基哌嗪合成路线图解

２，６┐二甲基哌嗪合成路线图解ＧＲＡＰＨＩＣＡＬＳＹＮＴＨＥＴＩＣＲＯＵＴＥＳＯＦ２，６┐ＤＩＭＥＴＨＹＬＰＩＰＥＲＡＺＩＮＥ戚建军郭惠元（中国医学科学院，中国协和医科大学医药生物技术研究所，北京１０００５０）ＱＩＪｉａｎ－Ｊｕｎ，ＧＵＯＨｕｉ－Ｙｕ...     

链状多胺的末端芳基化

链状多胺的末端芳基化ＳｃｉａｆａｎｉＪＡ等［ＪＯｒｇＣｈｅｍ，１９９６；６１：３２２１］链状多胺Ｈ２ＮＣＨ２（ＣＨ２ＮＨＣＨ２）ｎＣＨ２ＮＨ２（ｎ＝１～３）与２当量的芳醛在氯仿溶液中反应，两端形成芳基亚胺，反应条件视芳醛而定。亚胺不经分离，以过量Ｎａ...     

Antioxidant activities of α-methyl-4-(3-oxo-2H-1,2-benzoisoselenazol-2-yl)benzeneacetic acid in vitro

Ａｎｔｉｏｘｉｄａｎｔａｃｔｉｖｉｔｉｅｓｏｆα┐ｍｅｔｈｙｌ┐４┐（３┐ｏｘｏ┐２Ｈ┐１，２┐ｂｅｎｚｏｉｓｏｓｅｌｅｎａｚｏｌ┐２┐ｙｌ）ｂｅｎｚｅｎｅａｃｅｔｉｃａｃｉｄｉｎｖｉｔｒｏＺＥＮＧＨｕａ－Ｗｕ，ＪＩＡＮＧＹｕａｎ－Ｙｉｎｇ１，ＣＡＩ...     

2－甲基－5－巯基－1，3，4－噻二唑的合成

２－甲基－５－巯基－１，３，４－噻二唑的合成李敬芬，王旭，黄剑（佳木斯医学院药学系黑龙江１５４００２）ＳＹＮＴＨＥＳＩＳＯＦ２－ＭＥＴＨＹＬ－５－ＭＥＲＣＡＰＴＯ－１，３，４－ＴＨＩＡＤＩＡＺＯＬＥ￥ＬＩＪｉｎｇ－Ｆｅｎ；ＷＡＮＧＸｕ；ＨＵＡＮＧＪｉ...     

Synthesis of potential aldose reductase inhibitors based on minimal pharmacophore requirements.

A series of 17 compounds were synthesized based on the premise that the minimal pharmacophore for aldose reductase inhibition requires the presence of both an aryl group and polar group connected by a linking structure. Three groups of compounds were synthesized, the first possessing an aniline-4-(2'-6'-methylbenzothiazole) or 2-aminobenzothiazole group as the aryl group, the second possessing a 2-naphthyl as the aryl group and the third possessing either a 4-(2-phenylthiazole) or 2-(5-2'-nitrophenylfuran) as the aryl group. In all three of these groups the carboxylate or its methyl ester are linked to the aryl group through various lengths of methylene carbons and amide or cinnamide groups. Optimal activity was observed when the carboxylic group was separated from the aryl group by a linking structure of five atoms in length. Both a double bond and an amide moiety are well tolerated in the linking structure.     

Functional characterization of human N-acetyltransferase 2 (NAT2) single nucleotide polymorphisms

N-Acetyltransferase 2 (NAT2) catalyses the activation and/or deactivation of a variety of aromatic amine drugs and carcinogens. Polymorphisms in the N-acetyltransferase 2 (NAT2) gene have been associated with a variety of drug-induced toxicities, as well as cancer in various tissues. Eleven single nucleotide polymorphisms (SNPs) have been identified in the NAT2 coding region, but the specific effects of each of these SNPs on expression of NAT2 protein and N-acetyltransferase enzymatic activity are poorly understood. To investigate the functional consequences of SNPs in the NAT2 coding region, reference NAT2*4 and NAT2 variant alleles possessing one of the 11 SNPs in the NAT2 coding region were cloned and expressed in yeast (Schizosaccharomyces pombe). Reductions in catalytic activity for the N-acetylation of a sulfonamide drug (sulfamethazine) and an aromatic amine carcinogen (2-aminofluorene) were observed for NAT2 variants possessing G191A (R64Q), T341C (I114T), A434C (E145P), G590A (R197Q), A845C (K282T) or G857A (G286T). Reductions in expression of NAT2 immunoreactive protein were observed for NAT2 variants possessing T341C, A434C or G590A. Reductions in protein stability were noted for NAT2 variants possessing G191A, A845C, G857A or, to some extent, G590A. No significant differences in mRNA expression or transformation efficiency were observed among any of the NAT2 alleles. These results suggest two mechanisms for slow acetylator phenotype(s) and more clearly define the effects of individual SNPs on human NAT2 expression, stability and catalytic activity.     

Natural products syntheses based on the biotransformation using biocatalyst

This review summarizes the chemoenzymatic synthesis of the biologically active natural products based on a combination of chemical diastereoselectivity and enzymatic enantioselectivity using biocatalyst. Asymmetric reduction of 2-methyl-3-keto ester with yeast gave the optically active syn-2-methyl-3-hydroxy ester, which was converted to natural product such as (-)-oudemansin B. Asymmetric hydrolysis of 3-acetoxy-2-methy esters possessing syn- or anti-structure afforded the optically active 3-hydroxy-2-methyl esters and 3-acetoxy-2-methy esters corresponding to the starting material. One of these optically active 3-hydroxy-2-methyl esters was converted to aglycone of macrolide, venturicidins A and B possessing 10 chiral centers. Both primary alcohols possessing a chiral center at β-position of hydroxyl group and secondary alcohols were subjected to the lipase-assisted acylation in the presence of acyl donor to afford the optically active esters and the optically active alcohols corresponding to the starting material. These optically active compounds were converted to the biologically active natural products such as bisabolane type sesquiterpenes, decaline type diterpenes or triterpenes, nikkomycin B, (+)-asperlin, (-)-chuangxinmycin, (-)-indolmycin, cystothiazoles melithiazols, myxothiazols and piericidins possessing antifungal and cytotoxicic activities, inhibition of NADH oxidation, etc. Reaction of primary alcohol and glucose using immobilized β-glucosidase gave alkyl β-glucosides in high yield. Pentaacetate of allyl β-glucoside was subjected to Mizoroki-Heck type reaction with phenylboronic acid derivatives to give phenylpropenoid β-D-glucopyranosid congeners.     

Uptake of cyclic dipeptide by PEPT1 in Caco-2 cells: phenolic hydroxyl group of substrate enhances affinity for PEPT1

Uptake of cyclic dipeptides by H+/oligopeptide cotransporter (PEPT1) was studied in monolayers of the human intestinal cell line, Caco-2. The cyclic dipeptides studied were cyclic glycylphenylalanine (cyclo(Gly-Phe)), cyclic phenylalanylserine (cyclo(Phe-Ser)), cyclic seryltyrosine (cyclo(Ser-Tyr)) and cyclic glycyltyrosine (cyclo(Gly-Tyr)). These molecules have both peptide bonds and aromatic rings, and are similar in structure to cephalexin and cephadroxil, which are transported by PEPT1. Cellular uptake of these cyclic dipeptides was pH dependent, and was inhibited by the addition of PEPT1 substrates such as glycylsarcosine, indicating PEPT1-mediated transport. Michaelis constants (Km) for these cyclic dipeptides were cyclo(Ser-Tyr) < cyclo(Phe-Ser), and cyclo(Gly-Tyr) < cyclo(Gly-Phe), indicating that tyrosine possessing phenol moiety has higher affinity for PEPT1 than phenylalanine possessing benzen moiety. The Km for cephadroxil possessing phenol moiety was reportedly lower than that for cephalexin possessing benzen moiety. Therefore, it was concluded that the phenolic hydroxyl group of the substrate may enhance affinity for PEPT1.     

Design,synthesis, and structure-activity relationship studies of novel 6,7-locked-[7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta]-2,4,6-trienoic acids

Retinoid X receptor:peroxisome proliferative-activated receptor (RXR:PPAR) heterodimers play a critical role in the regulation of glucose (RXR/PPARgamma) and lipid metabolism (RXR/PPARalpha). Previously, we described a concise structure-activity relationship study of selective RXR modulators possessing a (2E,4E,6Z)-3-methyl-7-(3,5-dialkyl-6-alkoxyphenyl)-octa-2,4,6-trienoic acid scaffold. These studies were focused on the 2-position alkoxy side chain. We describe here the design and synthesis of a novel series of RXR selective modulators possessing the same aromatic core structure with the addition of a ring locked 6-7-Z-olefin on the trienoic acid moiety. The synthesis and structure-activity relationship studies of these 6,7-locked cyclopentenyl, phenyl, thienyl, furan, and pyridine-trienoic acid derivatives is presented herein.     

Antifungal cyclic peptides from the terrestrial blue-green alga Anabaena laxa. II. Structures of laxaphycins A, B, D and E.

Laxaphycins A and B are the major components in an antifungal mixture of cyclic peptides from the terrestrial blue-green alga Anabaena laxa FK-1-2. NMR and MS spectral studies coupled with amino acid analysis indicate that the gross structures of laxaphycins A and B are cyclic (Aoc-Hse-E-Dhb-Hyp-Hse-Phe-Leu-Ile-Ile-Leu-Gly) where Aoc is a 3-aminooctanoic acid residue and cyclic (Ala-Hleu-Gln-N-MeIle-Hasn-Thr-Pro-Leu-Thr-Ade-Val- Hleu) where Ade is a 3-aminodecanoyl unit, respectively. Laxaphycin E, a minor cyclic undecapeptide, differs in gross structure from laxaphycin A in possessing a 3-aminodecanoic acid unit (Ade) in lieu of Aoc, whereas laxaphycin D, a minor cyclic dodecapeptide, differs from laxaphycin B in possessing a 3-aminooctanoyl unit (Aoc) instead of an Ade unit.     

2-Heteroaryl 2-Substituted Phenylketone Derivatives and Their Inhibitory Activity on Platelet Aggregation

R 68070 and CV-4151 are two compounds possessing both thromboxane synthetase inhibitory activity and thromboxane receptor antagonist properties. 2-Heteroaryl 2-substituted phenylketone derivatives with a partial structural similarity to R 68070 and CV-4151, i.e. possessing a phenyl and a heteroaryl moiety, have been prepared and found to have antiplatelet activity. The compound 2-thienyl 2′-hydroxyphenyl ketone (4) was shown to completely inhibit platelet aggregation induced by arachidonic acid at a concentration of 5·0 μm . Structure-activity analysis indicated that the presence of a ketone group is an important requirement for this inhibitory activity. An o-hydroxyl substitution on the phenyl ring, and a 2-thienyl of heteroaryl ring might increase inhibitory activity.     

Cytotoxicity of lissoclibadins and lissoclinotoxins, isolated from a tropical ascidian Lissoclinum cf. badium, against human solid-tumor-derived cell lines

The in vitro growth inhibitory activity of lissoclibadins and lissoclinotoxins isolated from the tropical ascidian Lissoclinum cf. badium against nine human cancer cell lines was examined to evaluate their potential anticancer efficacy. Lissoclibadins 1 (1) and 2 (2), and lissoclinotoxin F (4) showed the strongest activity of the six compounds tested, which were more potent than the anticancer drug cisplatin. Compound 1 has a trimeric structure, and compounds 2 and 4 are structural isomers possessing dimeric structures connected by disulfide and sulfide bonds of trans- and cis-orientations, respectively. Lissoclibadin 3 (3), a dimeric compound connected by two sulfide bonds, and two monomeric compounds (5, 6) were less active than 1, 2, and 4. Lissoclibadin 2 (2) was the most interesting compound possessing potent inhibitory activity against colon (DLD-1 and HCT116), breast (MDA-MB-231), renal (ACHN), and non-small-cell lung (NCI-H460) cancer cell lines and showing no toxicity following a 50 mg/kg single treatment to mice, and preferable stability in rat plasma.     

Synthesis and antifungal activity of naturally occurring O- and C-prenylated flavanones

Flavonoids is one of the most important groups of naturally occurring O-heterocycles possessing a wide range of biological activity. O- and C-prenylated flavanones as members of flavonoids also show remarkable biological activity such as antibacterial, antiviral, anti-tumor, antifungal, anti-HIV and enzyme inhibition activity. O- and C-prenylated flavanones possessing remarkable biological activity are representatives of this family of natural products. In this paper efficient synthetic methods have been reported for the preparation of O-(2, 3) and C-(4, 5) prenylated flavanones isolated from Monotes engleri and their analogues (26-30; 38-43) starting from commercially available starting materials. In vitro pharmacological examinations of our compounds were performed on different Candida species (Candida albicans, Candida inconspicua, Candida dubliniensis, Candida krusei) by agardiffusion method. Our structure-activity relationship study clearly showed that any modification of the structure of selinone (2) and monotesone-A (3) led to the total loss the fungistatic activity.     

Synthesis of 3'- and 5'-nitrooxy pyrimidine nucleoside nitrate esters: "nitric oxide donor" agents for evaluation as anticancer and antiviral agents

A group of 3'-O-nitro-2'-deoxyuridines, 3'-O-nitro-2'-deoxycytidines, and 5'-O-nitro-2'-deoxyuridines possessing a variety of substituents (H, Me, F, I) at the C-5 position were synthesized for evaluation as anticancer/antiviral agents that have the ability to concomitantly release cytotoxic nitric oxide (*NO). Although these compounds generally released a greater percent of *NO than the reference drug isosorbide dinitrate upon incubation in the presence of l-cysteine, or serum, their cytotoxicity (CC(50) = 10(-3) to 10(-6) M range) was comparable to 5-iodo-2'-deoxyuridine, but weaker than 5-fluoro-2'-deoxyuridine, against a variety of cancer cell lines. No differences in cytotoxicity against nontransfected (KBALB, 143B), and the corresponding transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK(+)) were observed, indicating that expression of the viral TK enzyme did not provide a gene therapeutic effect. These nitrate esters were inactive antiviral agents except for 5-iodo-3'-O-nitro-2'-deoxyuridine that showed modest activity against HSV-1, HSV-2, and vaccinia virus.