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151.
152.
Vijeta Sharma Nagarjuna Amarnath Swapnil Shukla R. Ayana Naveen Kumar Nisha Yadav Deepika Kannan Seema Sehrawat Soumya Pati Bimlesh Lochab Shailja Singh 《Bioorganic & medicinal chemistry letters》2018,28(9):1629-1637
Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na+ levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490?nM from 17.54?µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action. 相似文献
153.
P. Gunasekaran G. Mukundan R. Kannan S. Velmurugan N. Aït-Abdelkader E. Alvarez-Macarie J. Baratti 《Biotechnology letters》1995,17(6):635-642
Summary The Zymomonas mobilis gene sacB that encodes the extracellular levansucrase was cloned and expressed in Escherichia coli. The gene product exhibited both sucrose hydrolysis activity and levan forming capability. Sub-cellular fractionation of E. coli carrying pLSS41 revealed that about 95% of the total sucrase activity was detected in the cytoplasmic fraction. The levansucrase gene was overexpressed (about hundred fold) in E. coli under T7 polymerase expression system. Nucleotide sequence analysis of this gene revealed an open reading frame of 1269 bp long coding for a protein of 423 amino acids with a molecular mass of 46.7 KDa. The deduced amino acid sequence was identical to the N-terminal amino acids of protein A51 of Z. mobilis ZM4. Therefore, the product of sacB is levansucrase. This is the first extracellular enzyme of Z. mobilis sequenced which does not possess a signal sequence. This gene is located 198 bp upstream of sacC gene encoding for the extracellular sucrase forming a gene cluster 相似文献
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Kannan Natarajan Jiansheng Jiang David H. Margulies 《Critical reviews in biochemistry and molecular biology》2019,54(2):164-173
Recognition of foreign and dysregulated antigens by the cellular innate and adaptive immune systems is in large part dependent on the cell surface display of peptide/MHC (pMHC) complexes. The formation of such complexes requires the generation of antigenic peptides, proper folding of MHC molecules, loading of peptides onto MHC molecules, glycosylation, and transport to the plasma membrane. This complex series of biosynthetic, biochemical, and cell biological reactions is known as “antigen processing and presentation”. Here, we summarize recent work, focused on the structural and functional characterization of the key MHC-I-dedicated chaperones, tapasin, and TAPBPR. The mechanisms reflect the ability of conformationally flexible molecules to adapt to their ligands, and are comparable to similar processes that are exploited in peptide antigen loading in the MHC-II pathway. 相似文献
157.
Studies on human and animal models of retinal dystrophy have suggested that apoptosis may be the common pathway of photoreceptor cell death. Autophagy, the major cellular degradation process in animal cells, is important in normal development and tissue remodeling, as well as under pathological conditions. Previously we provided evidence that genes, whose products are involved in apoptosis and autophagy, may be coexpressed in photoreceptors undergoing degeneration. Here, we investigated autophagy in oxidative stress-mediated cell death in photoreceptors, analyzing the light-damage mouse model and 661W photoreceptor cells challenged with H(2)O(2). In the in vivo model, we demonstrated a time-dependent increase in the number of TUNEL-positive cells, concomitant with the formation of autophagosomes. In vitro, oxidative stress increased mRNA levels of apoptotic and autophagic marker genes. H(2)O(2) treatment resulted in the accumulation of TUNEL-positive cells, the majority of which contain autophagosomes. To determine whether autophagy and apoptosis might precede each other or co-occur, we performed inhibitor studies. The autophagy inhibitor 3-methyladenine (3-MA), silencing RNA (siRNA) against two genes whose products are required for autophagy (autophagy-related (ATG) gene 5 and beclin 1), as well as the pan-caspase-3 inhibitor, Zvad-fmk, were both found to partially block cell death. Blocking autophagy also significantly decreased caspase-3 activity, whereas blocking apoptosis increased the formation of autophagosomes. The survival effects of 3?MA and zVAD-fmk were not additive; rather treatment with both inhibitors lead to increased cell death by necrosis. In summary, the study first suggests that autophagy participates in photoreceptor cell death possibly by initiating apoptosis. Second, it confirms that cells that normally die by apoptosis will execute cell death by necrosis if the normal pathway is blocked. And third, these results argue that the up-stream regulators of autophagy need to be identified as potential therapeutic targets in photoreceptor degeneration. 相似文献
158.
Sarah A Hansen Michael K Fink Anandhi Upendran Cynthia L Besch-Williford Robert S Livingston James M Amos-Landgraf Jimmy C Lattimer Raghuraman Kannan 《Comparative medicine》2015,65(5):424-428
A socially-housed New Zealand white rabbit presented with a large subcutaneous mass on the ventral thorax approximately 11 mo after the intrahepatic delivery of a suspension of VX2 carcinoma cells to induce hepatocellular carcinoma as part of a nanoparticle study. The mass and closely associated axillary lymph node were removed en bloc. Immunohistochemical staining identified the mass as an undifferentiated carcinoma. The rabbit demonstrated no appreciable pathology at the study end point at 16 mo after VX2 inoculation. An additional rabbit from the same VX2 injection cohort was found at necropsy to have an unanticipated intraabdominal mass, also identified as an undifferentiated carcinoma. This case report summarizes the molecular analysis of both tumors through a novel PCR assay, which identified the delayed and aberrant onset of VX2 carcinoma in an extended timeframe not previously reported.Abbreviations: CRPV, cottontail rabbit papillomavirusThe VX2 squamous cell carcinoma cell line was developed in 1938 from cells isolated from a domestic rabbit with a Shope papillomavirus-induced skin papilloma.11,16 The inoculation of allogenic adult rabbits with the VX2 tumor cells results in a wholly anaplastic carcinoma that grows rapidly and forms frequent metastases.7,11 Molecular analysis of the VX2 carcinoma has revealed multiple integrated copies of highly methylated cottontail rabbit papilloma virus (CRPV) genomic material.5-7,17 For decades, the rabbit VX2 carcinoma has supported oncology research by providing a large animal model that supports the investigation of neoplasms of diverse tissues including liver, lung, pleural space, muscle, and bone.9,12,15,18,19 Benefits of this model include relatively simple inoculation, rapid growth with local tissue invasion, predictable metastases, and reproducibility.3,4,13,14 In the current report, we describe the use of VX2 cells intended to induce a hepatic carcinoma model in rabbits and the unexpected outcomes associated with the model. 相似文献
159.
Investigation of Optical Spectroscopic and Computational Binding Mode of Bovine Serum Albumin with 1, 4‐Bis ((4‐((4‐Heptylpiperazin‐1‐yl) Methyl)‐1H‐1, 2, 3‐Triazol‐1‐yl) Methyl) Benzene 下载免费PDF全文
Subramani Karthikeyan Shanmugavel Chinnathambi Ayyavoo Kannan Perumal Rajakumar Devadasan Velmurugan Ganesan Bharanidharan Prakasarao Aruna Singaravelu Ganesan 《Journal of biochemical and molecular toxicology》2015,29(8):373-381
A newly synthesized 1, 4‐bis ((4‐((4‐heptylpiperazin‐1‐yl) methyl)‐1H‐1, 2, 3‐triazol‐1‐yl) methyl) benzene from the family of piperazine derivative has good anticancer activity, antibacterial and low toxic nature; its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of piperazine derivative to bovine serum albumin (BSA) was investigated using fluorescence spectroscopy. The molecular distance r between the donor (BSA) and acceptor (piperazine derivative) was estimated according to Forster's theory of nonradiative energy transfer. The physicochemical properties of piperazine derivative, which induced structural changes in BSA, have been studied by circular dichroism and those chemical environmental changes were probed using Raman spectroscopic analysis. Further, the binding dynamics was expounded by synchronous fluorescence spectroscopy and molecular modeling studies explored the hydrophobic interaction and hydrogen bonding results, which stabilize the interaction. 相似文献