共查询到20条相似文献,搜索用时 0 毫秒
1.
DNA aptamers as potential anti-HIV agents 总被引:3,自引:0,他引:3
Guanine (G)-rich DNA sequences can adopt stable G-quadruplex structures by G-tetrad hydrogen-bonding and hydrophobic stacking. Recently, it has been shown that a DNA sequence forms an aptamer (termed 93del) and adopts a novel dimeric quadruplex folding topology in K+ solution. This aptamer exhibits anti-HIV1 integrase activity in the nanomolar range in vitro. A docking-based model of the 93del-integrase complex positions the DNA aptamer within a channel of the tetrameric integrase. This mutual fitting blocks several catalytic amino acid residues that are essential for integrase function, and accounts for the anti-HIV1 activity of the 93del aptamer. 相似文献
2.
3.
Reaction of nordihydroguaiaretic acid with various alkyl chloride, 1-piperidinecarbonyl chloride, methyl chloroformate, or 1,1'-carbonyldiimidazole under alkaline conditions produced the corresponding phenol ethers, carbamates and carbonates, respectively, in 67-83% yields. Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found stable in aqueous solution. These new compounds exerted appealing activity against HIV Tat-regulated transactivation in human epithelial cells. The most potent compound meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperdino)ethoxyphenyl])butane tetrakishydrochloride salt (5b) showed IC(50) value of 0.88 microM. 相似文献
5.
6.
Plants as a source of anti-cancer and anti-HIV agents 总被引:2,自引:0,他引:2
Plant‐derived compounds have played an important role in the development of several clinically useful anti‐cancer agents. These include vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, etoposide, and paclitaxel (Taxol®). Several promising new agents are in clinical development based on selective activity against cancer‐related molecular targets, including flavopiridol and Combretastatin A4 phosphate. Recently, plants have yielded several agents showing anti‐AIDS activity, and one of these, (+)‐calanolide A, is in clinical development. 相似文献
7.
Paolo Di Gianvincenzo Marco Marradi Olga María Martínez-Ávila Luis Miguel Bedoya José Alcamí Soledad Penadés 《Bioorganic & medicinal chemistry letters》2010,20(9):2718-2721
Gold nanoparticles coated with multiple copies of an amphiphilic sulfate-ended ligand are able to bind the HIV envelope glycoprotein gp120 as measured by surface plasmon resonance (SPR) and inhibit in vitro the HIV infection of T-cells at nanomolar concentrations. A 50% density of sulfated ligands on ~2 nm nanoparticles (the other ligands being inert glucose derivatives) is enough to achieve high anti-HIV activities. This result opens up the possibility of tailoring both sulfated ligands and other anti-HIV molecules on the same gold cluster, thus contributing to the development of non-cocktail based multifunctional anti-HIV systems. 相似文献
8.
Cheng P Huang N Jiang ZY Zhang Q Zheng YT Chen JJ Zhang XM Ma YB 《Bioorganic & medicinal chemistry letters》2008,18(7):2475-2478
A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening revealed that 6,7-dihydroxytetrahydroisoquinolines possessed higher selective index than 6,7-dimethoxyl analogs due to the significantly decreased cytotoxicities. Compounds 6, 24, and 36 showed potent anti-HIV activities with EC(50) values of 8.2, 4.6, and 5.3microM respectively, and the cytotoxicities (CC(50)) of these three compounds were 784.3, 727.3, and 687.3microM, which resulted in SI values larger than 95, 159, and 130 respectively. 相似文献
9.
10.
Yoshimura Y Yamazaki Y Saito Y Natori Y Imamichi T Takahata H 《Bioorganic & medicinal chemistry letters》2011,21(11):3313-3316
As a part of our ongoing efforts to identify new anti-HIV agents, a 5′-thiopyrano-nucleoside derivative 4, designed based on 4′-thioD4C 1 and cyclohexenylnucleoside 3, was synthesized. The dihydrothiopyran skeleton of 4 was constructed by the ring closing metathesis of 21 which was synthesized from but-2-yne-1,4-diol. After converting the protecting group from MOM to TBS followed by oxidation, a Pummerer-type thioglycosylation reaction of 24 with persilylated uracil gave the desired 5-thiodihydrothiopyranyluracils 25 and 26 as a mixture of anomers. The conversion of 25 to a cytosine derivative and subsequent deprotection gave a 5-thiodidehydropyranosylcytosine derivative 4 in good yield. The anti-HIV activity of 4 was also evaluated. 相似文献
11.
John F. Miller Elizabeth M. Turner Kristjan S. Gudmundsson Stephen Jenkinson Andrew Spaltenstein Michael Thomson Pat Wheelan 《Bioorganic & medicinal chemistry letters》2010,20(7):2125-2128
The lead optimization of a series of N-substituted benzimidazole CXCR4 antagonists is described. Side chain modifications and stereochemical optimization led to substantial improvements in potency and protein shift to afford compounds with low nanomolar anti-HIV activity. 相似文献
12.
13.
Kashiwada Y Sekiya M Ikeshiro Y Fujioka T Kilgore NR Wild CT Allaway GP Lee KH 《Bioorganic & medicinal chemistry letters》2004,14(23):5851-5853
3-O-Acyl-betulin and -dihydrobetulin derivatives were prepared and evaluated for anti-HIV activity. 3-O-Glutaryl-dihydrobetulin (17) demonstrated extremely potent anti-HIV activity with an EC(50) value of 2 x 10(-5) microM and a TI value of 1.12 x 10(6). 3-O-(3',3'-Dimethylsuccinyl)- and 3-O-(3',3'-dimethylglutaryl)-dihydrobetulins (15, 16) were also potent anti-HIV compounds with EC(50) values of 0.0017 and 0.0013 microM, respectively, and TI values of 16,160 and 19,530, respectively. 相似文献
14.
Juan Xiong Yoshiki Kashiwada Chin-Ho Chen Keduo Qian Susan L. Morris-Natschke Kuo-Hsiung Lee Yoshihisa Takaishi 《Bioorganic & medicinal chemistry》2010,18(17):6451-6469
Fourteen novel conjugates of 3,28-di-O-acylbetulins with AZT were prepared as anti-HIV agents, based on our previously reported potent anti-HIV triterpene leads, including 3-O-acyl and 3,28-di-O-acylbetulins. Nine of the conjugates (49–53, 55, 56, 59, and 60) exhibited potent anti-HIV activity at the submicromolar level, with EC50 values ranging from 0.040 to 0.098 μM in HIV-1NL4-3 infected MT-4 cells. These compounds were equipotent or more potent than 3-O-(3′,3′-dimethylsuccinyl)betulinic acid (2), which is currently in Phase IIb anti-AIDS clinical trial. 相似文献
15.
Kashiwada Y Chiyo J Ikeshiro Y Nagao T Okabe H Cosentino LM Fowke K Lee KH 《Bioorganic & medicinal chemistry letters》2001,11(2):183-185
Four isomers of 3,28-di-O-(dimethylsuccinyl)-betulin were prepared and evaluated for anti-HIV activity against HIV-1 replication in H9 lymphocyte cells. 3-O-(3',3'-Dimethylsuccinyl)-28-O-(2", 2"-dimethvlsuccinyl)-betulin (11) was the most potent anti-HIV compound with an EC5, value of 0.00087 microM and a TI value of 42,400. 相似文献
16.
P Xia Z Y Yang Y Xia Y Q Zheng L M Cosentino K H Lee 《Bioorganic & medicinal chemistry》1999,7(9):1907-1911
In our search for novel anti-HIV agents, seven 17-carboxylated steroid derivatives were synthesized and evaluated as potential anti-HIV agents. Compound 13 exhibited potent anti-HIV activity in acutely infected H9 lymphocytes with EC50 and therapeutic index values of 0.8 microM and 300, respectively. 相似文献
17.
《Bioorganic & medicinal chemistry》2016,24(20):4768-4778
18.
Bonnard V Pascale L Azoulay S Di Giorgio A Rogez-Kreuz C Storck K Clayette P Patino N 《Bioorganic & medicinal chemistry》2010,18(21):7432-7438
Based on a split-and-mix strategy, a library of trimeric Polyamide Amino Acids (PAA) incorporating four different amino acids (Lys, Ala, Arg, and Phe) has been prepared. Screening of the batches for HIV TAR RNA binding in a fluorescent assay allowed the identification of several components that interact with TAR RNA at a micromolar concentration, with a good TAR versus tRNA specificity. Some of these compounds compete efficiently with the association of TAR and Tat protein. In cell cultures, these compounds display a moderate antiviral activity, associated nevertheless with some toxicity. Overall, these results confirm that this new family can be a basis for the design of novel RNA targeting drugs. 相似文献
19.
《Bioorganic & medicinal chemistry letters》2014,24(3):817-820
A series of α- and β-carboxylated phospholipid prodrugs of dideoxy nucleosides have been synthesized and evaluated against HIV. An increase in biological effect with a factor of 500 has only been observed for the adenine nucleoside, which suggests that this prodrug approach is base specific. 相似文献
20.
Sheng-Jiao Yan Han Zheng Chao Huang Yu-Yun Yan Jun Lin 《Bioorganic & medicinal chemistry letters》2010,20(15):4432-4435
Novel polyhalo 2,4-diaminoquinazolines 3a–3d were prepared by reacting polyhaloisophthalonitriles with guanidine carbonate under solvent-free conditions and in the absence of a catalyst with good yields (74–95%). A series of highly functionalized 2,4-diaminoquinazolines 4–5 were then synthesized based on 3a–3c. The anticancer activities of compounds 3–5 were evaluated in vitro against human cell lines such as Skov-3, HL-60, A431, A549, and HepG-2. Some of the compounds showed excellent cytotoxic activity and 5a was found to be the most potent derivative, with an IC50 value lower than 2.5 μg/mL against the five tumor cell lines, making it more active than cisplatin. Representative compounds were also preliminarily evaluated as HIV-1 inhibitors in vitro, and 3c showed the most potent anti-HIV-1 activity with EC50 values of 0.6 and 1.6 μg/mL, and TI values of >59.6 and 66.6, respectively. 相似文献