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941.
Reddy BV Rajeswari N Sarangapani M Roopa Reddy G Madan Ch Pranay Kumar K Srinivasa Rao M 《Bioorganic & medicinal chemistry letters》2011,21(21):6510-6514
Indole and its derivatives undergo smooth conjugate addition onto en-1,4-dione derived from isatin and acetophenone, in the presence of a catalytic amount of molecular iodine in acetonitrile under mild conditions to afford a novel class of 3-(1-(1H-indol-3-yl)-2-oxo-2-phenylethyl)indolin-2-one derivatives in good yields with high degree of 1,4-selectivity. Some of these compounds are found to exhibit modest antibacterial and antifungal properties. 相似文献
942.
Rao VK Chhikara BS Shirazi AN Tiwari R Parang K Kumar A 《Bioorganic & medicinal chemistry letters》2011,21(12):3511-3514
An efficient and economical method was developed for the synthesis of 3-substituted indoles by one-pot three-component coupling reaction of a substituted or unsubstituted benzaldehyde, N-methylaniline, and indole or N-methylindole using Yb(OTf)3-SiO2 as a catalyst. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. The 4-methylphenyl (4o and 4p) and 4-methoxyphenyl (4q) indole derivatives inhibited the cell proliferation of SK-OV-3 and HT-29 cells by 70-77% at a concentration of 50 μM. The unsubstituted phenyl (4d) and 3-nitrophenyl (4l) derivatives showed the inhibition of c-Src kinase with IC50 values of 50.6 and 58.3 μM, respectively. 相似文献
943.
McGuigan C Madela K Aljarah M Gilles A Battina SK Ramamurty CV Srinivas Rao C Vernachio J Hutchins J Hall A Kolykhalov A Henson G Chamberlain S 《Bioorganic & medicinal chemistry letters》2011,21(19):6007-6012
We have previously reported the power of combining a 5'-phosphoramidate ProTide, phosphate pro-drug, motif with a 6-methoxy purine pro-drug entity to generate highly potent anti-HCV agents, leading to agents in clinical trial. We herein extend this work with the disclosure that a variety of alternative 6-substituents are tolerated. Several compounds exceed the potency of the prior 6-methoxy leads, and in almost every case the ProTide is several orders of magnitude more potent than the parent nucleoside. We also demonstrate that these agents act as pro-drugs of 2'-C-methyl guanosine monophosphate. We have also reported the novel use of hepatocyte cell lysate as an ex vivo model for ProTide metabolism. 相似文献
944.
Jin CH Krishnaiah M Sreenu D Subrahmanyam VB Rao KS Mohan AV Park CY Son JY Sheen YY Kim DK 《Bioorganic & medicinal chemistry letters》2011,21(20):6049-6053
A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC(50) value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. 相似文献
945.
Thanigaimalai P Lee KC Sharma VK Rao EV Roh E Kim Y Jung SH 《Bioorganic & medicinal chemistry letters》2011,21(7):1922-1925
Chalcone type compound 1a ((E)-6′-benzylidene-4a′-methyl-4′,4a′,7′,8′-tetrahydro-3′H-spiro[[1,3]dithiolane-2,2′-naphthalen]-5′(6′H)-one) was discovered as an potent inhibitor in melanogenesis. To define its structure-activity relationship, a series of analogs 1b-n, dithiolane truncated 2a-b and ring A removed 3a-e were prepared and evaluated. The electron donating substitution on the phenyl ring (ring C) rather than an electron withdrawing group and dithiolane motif of 1 are needed for the activity enhancement. The scaffold containing both rings A and B associated with α,β-unsaturated system connected to phenyl of 1 was essential for antimelanogenesis. 相似文献
946.
Ponnada Suresh Kumar KK Pulicherla Mrinmoy Ghosh Anmol Kumar KRS Sambasiva Rao 《Bioinformation》2011,6(8):311-314
Enzymes from psychrophiles catalyze the reactions at low temperatures with higher specific activity. Among all the psychrophilic enzymes produced, cold active
β-galactosidase from marine psychrophiles revalorizes a new arena in numerous areas at industrial level. The hydrolysis of lactose in to glucose and galactose by
cold active β-galactosidase offers a new promising approach in removal of lactose from milk to overcome the problem of lactose intolerance. Herein we propose, a
3D structure of cold active β-galactosidase enzyme sourced from Pseudoalteromonas haloplanktis by using Modeler 9v8 and best model was developed having
88% of favourable region in ramachandran plot. Modelling was followed by docking studies with the help of Auto dock 4.0 against the three substrates lactose,
ONPG and PNPG. In addition, comparative docking studies were also performed for the 3D model of psychrophilic β-galactosidase with mesophilic and
thermophilic enzymes. Docking studies revealed that binding affinity of enzyme towards the three different substrates is more for psychrophilic enzyme when
compared with mesophilic and thermophilic enzymes. It indicates that the enzyme has high specific activity at low temperature when compared with mesophilic
and thermophilic enzymes. 相似文献
947.
Methicillin resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life threatening outbreaks such as community-onset and nosocomial infections has emerged as 'superbug'. The organism developed resistance to all classes of antibiotics including the best known Vancomycin (VRSA). Hence, there is a need to develop new therapeutic agents. This study mainly evaluates the potential use of botanicals against MRSA infections. Computer aided design is an initial platform to screen novel inhibitors and the data finds applications in drug development. The drug-likeness and efficiency of various herbal compounds were screened by ADMET and docking studies. The virulent factor of most of the MRSA associated infections are Penicillin Binding Protein 2A (PBP2A) and Panton-Valentine Leukocidin (PVL). Hence, native structures of these proteins (PDB: 1VQQ and 1T5R) were used as the drug targets. The docking studies revealed that the active component of Aloe vera, β-sitosterol (3S, 8S, 9S, 10R, 13R, 14S, 17R) -17- [(2R, 5R)-5-ethyl-6-methylheptan-2-yl] -10, 13-dimethyl 2, 3, 4, 7, 8, 9, 11, 12, 14, 15, 16, 17- dodecahydro-1H-cyclopenta [a] phenanthren-3-ol) showed best binding energies of -7.40 kcal/mol and -6.34 kcal/mol for PBP2A and PVL toxin, respectively. Similarly, Meliantriol (1S-1-[ (2R, 3R, 5R)-5-hydroxy-3-[(3S, 5R, 9R, 10R, 13S, 14S, 17S)-3-hydroxy 4, 4, 10, 13, 14-pentamethyl-2, 3, 5, 6, 9, 11, 12, 15, 16, 17-decahydro-1H-cyclopenta[a] phenanthren-17-yl] oxolan-2-yl] -2- methylpropane-1, 2 diol), active compound in Azadirachta indica (Neem) showed the binding energies of -6.02 kcal/mol for PBP2A and -8.94 for PVL toxin. Similar studies were conducted with selected herbal compound based on pharmacokinetic properties. All in silico data tested in vitro concluded that herbal extracts of Aloe-vera, Neem, Guava (Psidium guajava), Pomegranate (Punica granatum) and tea (Camellia sinensis) can be used as therapeutics against MRSA infections. 相似文献
948.
衰老是任何生物都无法避免的生理现象,它由多种因素引起,其过程极其复杂.酵母细胞是目前衰老研究领域公认的模式生物,一系列影响衰老的分子作用机理及调控因素的发现均源自于对酵母细胞的研究.自然衰老是酵母细胞的衰老模式之一,由于该衰老过程与其他高等真核细胞(特别是哺乳动物细胞)极为相似,近年来受到广泛关注.全面比较酵母细胞衰老的两种模式,详细介绍自然衰老过程中分子作用机理的研究进展,重点阐述其复杂的自然寿命调控通路,包括卡路里限制以及药物添加对Ras/PKA、Sch9、Tor等营养依赖型调控通路的影响,并展望未来该领域需要解决的重要科学问题,为全面深入了解高等生物,特别是人类自身的衰老机理提供参考. 相似文献
949.
本研究通过对新疆地区不明原因发热人群血清Tahyna病毒抗体进行检测,以了解Tahyna病毒在当地的感染状况及分布特征。通过间接免疫荧光方法对新疆维吾尔自治区南部喀什地区、北部伊犁地区742例不明原因发热患者急性期血清标本进行Tahyna病毒抗体检测,并对IgM抗体阳性标本平行进行Tahyna病毒、Snowshoe hare病毒和Inkoo病毒三种抗原性相似的布尼亚病毒的蚀斑减少中和试验。研究结果显示新疆南部喀什地区采集不明原因发热患者急性期血清中,IgM抗体阳性率5.3%,IgG抗体阳性率18.3%;新疆北部伊犁地区采集的急性期患者血清标本中并未发现TAHV IgM抗体阳性;蚀斑减少中和试验结果显示,TAHV IgM抗体阳性患者血清中Tahyna病毒中和抗体滴度较其它两种布尼亚病毒中和抗体滴度升高明显。本研究证实新疆南部地区不明原因发热人群存在Tahyna病毒的急性感染和既往感染,为相关疾病的进一步监测提供基础。 相似文献
950.
目的 研究 miR-125b在前列腺癌高低转移潜能细胞中的表达差异及其对高转移细胞株1E8细胞的运动转移中的作用和可能的分子机制.方法 realtime PCR法检测前列腺癌高低转移潜能配对细胞系中 miR-125b的表达差异.通过划痕实验及transwell实验观察1E8细胞及转染 miR-125b 抑制剂及其阴性对照后该细胞运动转移能力的变化.结果 realtime PCR结果显示高转移潜能1E8细胞中miR-125b表达水明显高于低转移潜能2B4细胞;下调miR-125b会减弱1E8细胞的运动转移能力.结论 miR-125b可促进前列腺癌细胞的运动转移能力. 相似文献