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181.
Inhibitory Activities of Butanol Fraction from Butea monosperma (Lam.) Taub. Bark Against Free Radicals,Genotoxins and Cancer Cells
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The present study was undertaken to investigate antioxidant, antigenotoxic, and antiproliferative activity of butanol fraction (Bmbu) from bark of medicinal plant Butea monosperma. Antioxidant potency of Bmbu was examined by various in vitro assays. It was also investigated for antigenotoxic activity using Escherichia coli. PQ37 employing SOS chromotest. Further, cytotoxic and apoptosis inducing activity of Bmbu was evaluated in MCF‐7 breast cancer cells. Bmbu showed potent free radical scavenging ability in ABTS assay (IC50 56.70 μg/ml) and anti‐lipid peroxidation ability (IC50 40.39 μg/ml). 4NQO and H2O2 induced genotoxicity was suppressed by Bmbu in SOS chromotest by 74.26% and 82.02% respectively. It also inhibited the growth of MCF‐7 cells with GI50 value of 158.71 μg/ml. Induction of apoptosis in MCF‐7 cells by Bmbu treatment was deciphered using confocal microscopy, flow cytometry, and neutral comet assay. Bmbu treatment increased cell population in sub‐G1 phase (69.6%) indicating apoptotic cells. Further, Bmbu treatment resulted in increased reactive oxygen species generation and decreased mitochondrial membrane potential indicating involvement of mitochondrial dependent pathway of apoptosis. HPLC profiling showed the presence of polyphenols such as ellagic acid, catechin, quercetin, and gallic acid as its major constituents. Consequently, it is suggested that the phytoconstituents from this plant may be further exploited for development of novel drug formulation with possible therapeutic implication. 相似文献
182.
R. Kenchappa Yadav D. Bodke Sandeep Telkar M. Aruna Sindhe 《Journal of chemical biology》2017,10(1):11-23
A novel series of thiazolo[3,2-a]benzimidazole derivatives containing benzofuran nucleus (5a–l) have been synthesized. The key intermediate, substituted benzimidazol-sulfanyl benzofuran ethanone (3a–d) was prepared by refluxing the mixture of substituted 2-acetyl benzofuran and substituted 2-mercaptobenzimidazole in acetic acid. The cyclisation of compounds (3a–d) using polyphosphoric acid furnished the corresponding 6-substituted benzofuran thiazolo[3,2-a]benzimidazoles (4a–d). Further, the cyclized compounds (4a–d) were subjected for Mannich reaction to give corresponding Mannich bases (5a–l). All newly synthesized compounds were screened for antifungal and anthelmintic activity. Amongst the tested compounds, 4b and 4d exhibited potential antifungal activity. From the anthelmintic activity data, it was found that the compounds 3a, 3b and 5i were found to be more effective against the tested earthworm Pheretima posthuma. In correlation to anthelmintic activity, the selected compounds were subjected for molecular docking studies and the compounds 3a and 5i have emerged as active anthelmintic agents with maximum binding affinity (?3.7 and ?5.4 kcal/mol). 相似文献
183.
Tripathi S Somashekar BS Mahdi AA Gupta A Mahdi F Hasan M Roy R Khetrapal CL 《Journal of biochemical and molecular toxicology》2008,22(2):119-127
The toxic effects of Al(3+) have been studied in 90-days AlCl(3) orally treated male albino rats (n = 7) using (1)H NMR spectroscopy-based metabolic profile of rat serum and urine, serum enzyme tests, behavioral impairment, and histopathology of kidney and liver. Metabolic profile of 90-days Al(3+)-treated rat sera showed significantly elevated levels of alanine, glutamine, beta-hydroxy-butyrate, and acetoacetate and significantly decreased level of acetone when compared with that of control rats. However, metabolic profile of 90-days Al(3+)-treated rat urine showed significantly decreased levels of citrate, creatinine, allantoin, trans-aconitate, and succinate and significantly increased level of acetate when compared to control rats. The overall perturbations observed in the metabolic profile of serum and urine demonstrate the impairment in the tricarboxylic acid cycle, liver and kidney metabolism, which was further reinstated by clinical chemistry and histopathological observations. Moreover, "in vivo" behavioral impairment has also been observed as the indication of aluminum neurotoxicity. 相似文献
184.
185.
The SarA protein family of Staphylococcus aureus 总被引:1,自引:0,他引:1
Cheung AL Nishina KA Trotonda MP Tamber S 《The international journal of biochemistry & cell biology》2008,40(3):355-361
Staphylococcus aureus is widely appreciated as an opportunistic pathogen, primarily in hospital-related infections. However, recent reports indicate that S. aureus infections can now occur in other wise healthy individuals in the community setting. The success of this organism can be attributed to the large array of regulatory proteins, including the SarA protein family, used to respond to changing microenvironments. Sequence alignment and structural data reveal that the SarA protein family can be divided into three subfamilies: (1) single domain proteins; (2) double domain proteins; (3) MarR homologs. Structural studies have also demonstrated that SarA, SarR, SarS, MgrA and thus possibly all members of this protein family are winged helix proteins with minor variations. Mutagenesis studies of SarA disclose that the winged helix motifs are important for DNA binding and function. Recent progress concerning the functions and plausible mechanisms of regulation of SarA and its homologs are discussed. 相似文献
186.
Kumar Srivastava B Soni R Patel JZ Jha S Shedage SA Gandhi N Sairam KV Pawar V Sadhwani N Mitra P Jain MR Patel PR 《Bioorganic & medicinal chemistry letters》2008,18(14):3882-3886
Facile synthesis of biaryl pyrazole sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716, 1) and an investigation of the effect of replacement of the –CO group in the compound 1 by the –SO2 group in the aminopiperidine region is reported. Primary ex-vivo pharmacological testing and in vitro screening of sulfonamide derivative 2 showed the loss of CB1 receptor antagonism. 相似文献
187.
Srivastava BK Soni R Joharapurkar A Sairam KV Patel JZ Goswami A Shedage SA Kar SS Salunke RP Gugale SB Dhawas A Kadam P Mishra B Sadhwani N Unadkat VB Mitra P Jain MR Patel PR 《Bioorganic & medicinal chemistry letters》2008,18(3):963-968
Design, synthesis and conformational analysis of few imidazole and oxazole as bioisosters of 4S-(-)-3-(4-chlorophenyl)-N-methyl-N'-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-caboxamidine (SLV-319) 2 is reported. Computer assisted conformational analysis gave a direct clue for the loss of CB1 antagonistic activity of the ligands without a fine docking simulation for the homology model. 相似文献
188.
The cold shock protein (CSP) from hyperthermophile Thermotoga maritima (TmCSP) is only marginally stable (DeltaG(T(opt)) = 0.3 kcal/mol) at 353 K, the optimum environmental temperature (T(opt)) for T. maritima. In comparison, homologous CSPs from E. coli (DeltaG(T(opt)) = 2.2 kcal/mol) and B. subtilis (DeltaG(T(opt)) = 1.5 kcal/mol) are at least five times more stable at 310 K, the T(opt) for the mesophiles. Yet at the room temperature, TmCSP is more stable (DeltaG(T(R)) = 4.7 kcal/mol) than its homologues (DeltaG(T(R)) = 3.0 kcal/mol for E. coli CSP and DeltaG(T(R)) = 2.1 kcal/mol for B. subtilis CSP). This unique observation suggests that kinetic, rather than thermodynamic, barriers toward unfolding might help TmCSP native structure at high temperatures. Consistently, the unfolding rate of TmCSP is considerably slower than its homologues. High temperature (600 K) complete unfolding molecular dynamics (MD) simulations of TmCSP support our hypothesis and reveal an unfolding scheme unique to TmCSP. For all the studied homologues of TmCSP, the unfolding process first starts at the C-terminal region and N-terminal region unfolds in the end. But for TmCSP, both the terminals resist unfolding for consistently longer simulation times and, in the end, unfold simultaneously. In TmCSP, the C-terminal region is better fortified and has better interactions with the N-terminal region due to the charged residues, R2, E47, E49, H61, K63, and E66, being in spatial vicinity. The electrostatic interactions among these residues are unique to TmCSP. Consistently, the room temperature MD simulations show that TmCSP is more rigid at its N- and C-termini as compared to its homologues from E. coli, B. subtilis, and B. caldolyticus. 相似文献
189.
Sandeep Rana Hyun-Seok Hong Lydia Barrigan Lee-Way Jin Duy H. Hua 《Bioorganic & medicinal chemistry letters》2009,19(3):670-674
The SβC gene is conditionally expressed a 99-residue carboxy terminal fragment, C99, of amyloid precursor protein in MC65 cells and causes cell death. Consequently, MC65 cell line was used to identify inhibitors of toxicity related to intracellular amyloid β (Aβ) oligomers. Compounds that reduce the level of Aβ peptides, prevent Aβ aggregation, or eliminate existing Aβ aggregates may be used in the treatment of Alzheimer’s disease (AD). Previously, we found that a tricyclic pyrone (TP) molecule, compound 1, prevents MC65 cell death and inhibits Aβ aggregation. Hence various TPs containing heterocycle at C7 side chain and a nitrogen at position 2 or 5 were synthesized and their MC65 cell protective activities evaluated. TPs containing N3′-adenine moiety such as compounds 1 and 11 are most active with EC50 values of 0.31 and 0.35 μM, respectively. EC50 values of tricyclic N5-analog, pyranoisoquinolinone 13, and N2-analog, pyranopyridinone 20, are 2.49 and 1.25 μM, respectively, despite the lack of adenine moiety. Further investigation of tricyclic N2- and N5-analogs is warranted. 相似文献