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排序方式: 共有223条查询结果,搜索用时 312 毫秒
181.
182.
Nagaraju GP Nalla AK Gupta R Mohanam S Gujrati M Dinh DH Rao JS 《Molecular cancer research : MCR》2011,9(1):51-66
Our previous work and that of other investigators strongly suggest a relationship between the upregulation of metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator receptor (uPAR) in tumor angiogenesis and metastasis. In this study, we evaluated the role of MMP-9 and uPAR in medulloblastoma cancer cell resistance to ionizing irradiation (IR) and tested the antitumor efficacy of siRNA (short interfering RNA) against MMP-9 [plasmid siRNA vector for MMP-9 (pM)] and uPAR [plasmid vector for uPAR (pU)] either alone or in combination [plasmid siRNA vector for both uPAR and MMP-9 (pUM)]. Cell proliferation (BrdU assay), apoptosis (in situ TUNEL for DNA fragmentation), and cell-cycle (FACS) analyses were carried out to determine the effect of siRNA either alone or in combination with IR on G2/M cell-cycle arrest in medulloblastoma cells. IR upregulated MMP-9 and uPAR expression in medulloblastoma cells; pM, pU, and pUM in combination with IR effectively reduced both MMP-9 and uPAR expression, thereby leading to increased radiosensitivity of medulloblastoma cells. siRNA treatments (pM, pU, and pUM) also promoted IR-induced apoptosis and enhanced IR-induced G2/M arrest during cell-cycle progression. While IR induces G2/M cell-cycle arrest through inhibition of the pCdc2- and cyclin B-regulated signaling pathways involving p53, p21/WAF1, and Chk2 gene expression, siRNA (pM, pU, and pUM) alone or in combination with IR induced G2/M arrest mediated through inhibition of the pCdc2- and cyclin B1-regulated signaling pathways involving Chk1 and Cdc25A gene expression. Taken together, our data suggest that downregulation of MMP-9 and uPAR induces Chk1-mediated G2/M cell-cycle arrest, whereas the disruption caused by IR alone is dependent on p53- and Chk2-mediated G2/M cell-cycle arrest. 相似文献
183.
E. Rajanarendar S. Ramakrishna K. Govardhan Reddy D. Nagaraju Y.N. Reddy 《Bioorganic & medicinal chemistry letters》2013,23(13):3954-3958
A new series of isoxazolyl-2,3-dihydrospiro[benzo[f]isoindole-1,3′-indoline]-2′,4,9-triones (14) were synthesized by reaction of 4-amino-3-methyl-5-styrylisoxazole 10 with chloroacetic acid followed by a three component reaction with substituted isatins 12 and 1,4-naphthoquinone 13 using Ceric ammonium nitrate (CAN) catalyst under aerial oxidation condition. Structures of these compounds were established on the basis of IR, 1H NMR, 13C NMR and mass spectral data. The title compounds 14a–j were evaluated for their anti-inflammatory and analgesic activity. Compounds 14d, 14e and 14f exhibited potent anti-inflammatory and analgesic activity as that of standard drugs. 相似文献
184.
Richa Nigam Kaki Raveendra Babu Topi Ghosh Bhavini Kumari Deepa Akula Subha Narayan Rath Prolay Das Roy Anindya Faiz Ahmed Khan 《Bioorganic & medicinal chemistry》2018,26(14):4100-4112
The mammalian AlkB homologue-3 (AlkBH3) is a member of the dioxygenase family of enzymes that in humans is involved in DNA dealkylation repair. Because of its role in promoting tumor cell proliferation and metastasis of cancer, extensive efforts are being directed in developing selective inhibitors for AlkBH3. Here we report synthesis, screening and evaluation of panel of arylated indenone derivatives as new class of inhibitors of AlkBH3 DNA repair activity. An efficient synthesis of 2,3-diaryl indenones from 2,3-dibromo indenones was achieved via Suzuki-Miyaura cross-coupling. Using a robust quantitative assay, we have obtained an AlkBH3 inhibitor that display specific binding and competitive mode of inhibition against DNA substrate. Finally, we established that this compound could prevent the proliferation of lung cancer cell line and enhance sensitivity to DNA damaging alkylating agent. 相似文献
185.
Settypalli Triloknadh Chunduri Venkata Rao Kerru Nagaraju Nallapaneni Hari Krishna Chintha Venkata Ramaiah Wudayagiri Rajendra Daggupati Trinath Yeguvapalli Suneetha 《Bioorganic & medicinal chemistry letters》2018,28(9):1663-1669
A series of thieno[2,3-d]pyrimidine alkyne Mannich base derivatives (7a-e, 8a-e) and thieno[2,3-d]pyrimidine 1,3,4-oxadiazole derivatives (9a-e, 10a-e) have been synthesized and evaluated for their neuroprotective and neurotoxicity activities where 9a, 10d displayed good neuroprotection 10.6 and 11.88?µg/mL respectively against the H2O2 induced cell death at the EC50 values and 9b, 9d showed respective toxic effects on PC12 cells at CC50 86.12 and 94.16?µg/mL. Compounds 9a, 9e, 10a and 10b showed strong antibacterial activity against two gram positive (S. aureus, B. subtilis) and two gram-negative strains (E. coli, P. aeruginosa) and showed good binding affinities with C(30) carotenoid dehydrosqualene synthase, Gyrase A and LpxC. This is the first report for the demonstration of thieno[2,3-d] pyrimidine derivatives as promising neuroprotective agents against H2O2 induced neurotoxicity on PC12 cells. 相似文献
186.
Nagaraju Marepu Sunandamma Yeturu Manojit Pal 《Bioorganic & medicinal chemistry letters》2018,28(20):3302-3306
The 1,2,3-triazole ring fused with pyridine/pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald’s strategy (i.e. C–N bond formation/reduction/diazotization/cyclization sequence) to the N-heteroarene system. Two of them showed promising antibacterial (comparable to streptomycin) and several showed potent antifungal (comparable to mancozeb) activities. 相似文献
187.
188.
Study on immune proteins in domesticated and wild silkmoths Bombyx mori and Antheraea mylitta, respectively, led to identification of a new class of antimicrobial proteins. We designated them as lysozyme-like proteins (LLPs) owing to their partial similarity with lysozymes. However, lack of characteristic catalytic amino acid residues essential for muramidase activity in LLPs puts them functionally apart from classical lysozymes. Two LLPs, one from B. mori (BLLP1) and the other from A. mylitta (ALLP1) expressed in a recombinant system, exhibited a broad-spectrum antibacterial action. Further investigation of the antibacterial mechanism revealed that BLLP1 is bacteriostatic rather than bactericidal against Escherichia coli and Micrococcus luteus. Substantial increase in hemolymph bacterial load was observed in B. mori upon RNA interference mediated in vivo knockdown of BLLP1. We demonstrate that the antibacterial mechanism of this protein depends on peptidoglycan binding unlike peptidoglycan hydrolysis or membrane permeabilization as observed with lysozymes and most other antimicrobial peptides. To our knowledge, this is the first report on functional analysis of novel, non-catalytic lysozyme-like family of antibacterial proteins that are quite apart functionally from classical lysozymes. The present analysis holds promise for functional annotation of similar proteins from other organisms. 相似文献
189.
Shiradkar MR Akula KC Dasari V Baru V Chiningiri B Gandhi S Kaur R 《Bioorganic & medicinal chemistry》2007,15(7):2601-2610
A novel clubbed triazolyl thiazole series of cdk5/p25 inhibitors, potentially useful for the treatment of Alzheimer's disease, is disclosed. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain cdk5/p25 and thus have potential as possible treatments for Alzheimer's disease. 相似文献
190.
Karumuri NN Gangireddy SR Narala VR Majee SS Gunwar S Reddy RC 《Biotechnology letters》2007,29(9):1333-1339
Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is used to treat full-thickness diabetic ulcers and is being
investigated for use in other chronic ulcers, non-healing wounds, and periodontal defects. A simple, novel method for expression
and purification of rhPDGF-BB from Escherichia coli is now described. This method produces the dimeric protein in high yield (10–12 mg/g wet cell mass) and with a purity >95%. rhPDGF-BB was exclusively
found in inclusion bodies (IBs) representing approx. 30% of the total cell proteins. The IBs were extracted and the monomer
purified by RP-HPLC. The purified rhPDGF-B monomer was then refolded using Tris buffer and subsequently dimerized to produce
biologically active rhPDGF-BB. This product was composed of two polypeptide chains, each approx. 12 kDa. The final product
exhibited specific activity in a fibroblast proliferation assay indistinguishable from that of the WHO reference standard. 相似文献