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1.
Shailesh Kumar Atma P. Dwivedi Vivek Kr. Kashyap A.K. Saxena A.K. Dwivedi Ranjana Srivastava Devi P. Sahu 《Bioorganic & medicinal chemistry letters》2013,23(8):2404-2407
Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 μg/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1× MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log10 reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition. 相似文献
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Shivalika Pathania Vinay Randhawa 《Journal of biomolecular structure & dynamics》2020,38(17):5108-5125
AbstractNipah Virus (NiV) is a newly emergent paramyxovirus that has caused various outbreaks in Asian countries. Despite its acute pathogenicity and lack of approved therapeutics for human use, there is an urgent need to determine inhibitors against NiV. Hence, this work includes prospection of potential entry inhibitors by implementing an integrative structure- and network-based drug discovery approach. FDA-approved drugs were screened against attachment glycoprotein (NiV-G, PDB: 2VSM), one of the prime targets to inhibit viral entry, using a molecular docking approach that was benchmarked both on CCDC/ASTEX and known NIV-G inhibitor set. The predicted small molecules were prioritized on the basis of topological analysis of the chemical-protein interaction network, which was inferred by integrating the drug-target network, NiV-human interaction network, and human protein-protein interaction network. A total of 17 drugs were predicted to be NiV-G inhibitors using molecular docking studies that were further prioritized to 3 novel leads???Nilotinib, Deslanoside and Acetyldigitoxin???on the basis of topological analysis of inferred chemical-protein interaction network. While Deslanoside and Acetyldigitoxin belong to an already known class of anti-NiV inhibitors, Nilotinib belongs to Benzenoids chemical class that has not been reported hitherto for developing anti-NiV inhibitors. These identified drugs are expected to be successful in further experimental evaluation and therefore could be used for anti-Nipah drug discovery. Apart, we also obtained various insights into the underlying chemical-protein interaction network, based on which several important network nodes were predicted. The applicability of our proposed approach was also demonstrated by prospecting for anti-NiV phytochemicals on an independent dataset.Communicated by Ramaswamy H. Sarma 相似文献
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Angiogenesis has a key role in the tumor progression and metastasis; targeting endothelial cell proliferation has emerged as a promising therapeutic strategy for the prevention of cancer. Previous studies have revealed a complex association between the process of angiogenesis and autophagy and its outcome on tumorigenesis. Autophagy, also known as type-II cell death, has been identified as an alternative way of cell killing in apoptotic-resistant cancer cells. However, its involvement in chemoresistance and tumor promotion is also well known. In this study, we used a derivate of natural product magnolol (Ery5), a potent autophagy inducer, to study the association between the autophagy and angiogenesis in both in vitro and in vivo model system. We found that the robust autophagy triggered by Ery5, inhibited angiogenesis and caused cell death independent of the apoptosis in human umbilical cord vein endothelial cells and PC-3 cells. Ery5 induced autophagy effectively inhibited cell proliferation, migration, invasion and tube formation. We further demonstrated that Ery5-mediated autophagy and subsequent inhibition of angiogenesis was reversed when autophagy was inhibited through 3-methyl adenine and knocking down of key autophagy proteins ATG7 and microtubule-associated protein light chain 3. While evaluating the negative regulation of autophagy on angiogenesis, it was interesting to find that angiogenic environment produced by the treatment of VEGF and CoCl2 remarkably downregulated the autophagy and autophagic cell death induced by Ery5. These studies, while disclosing the vital role of autophagy in the regulation of angiogenesis, also suggest that the potent modulators of autophagy can lead to the development of effective therapeutics in apoptosis-resistant cancer. 相似文献
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Sindhu Meenakshi Kumar Anil Yadav Honey Chaudhary Darshna Jaiwal Ranjana Jaiwal Pawan K. 《Plant Cell, Tissue and Organ Culture》2019,139(3):429-453
Plant Cell, Tissue and Organ Culture (PCTOC) - Cowpea (Vigna unguiculata (L.) Walp.) is a warm-season legume crop which is widely grown by resource-poor small and marginal farmers of Sub-Saharan... 相似文献
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Metallothionein (NIT) and zinc concentrations have been estimated in luminal fluids of caput/corpus and cauda epididymis and serum of zinc deficient (ZD), pairfed (PF) and control--ad libitum fed (ZC) groups of Wistar rats. MT decreased significantly in luminal fluids of caput corpus and cauda epididymis and serum of zinc deficient rats as compared to their respective controls. However, the decrease was non-significant in luminal fluids of corpus epididymis and serum of 4-weeks zinc deficient animals as compared to their control. Zinc levels also declined significantly in luminal fluids of epididymis and serum of zinc deficient rats as compared to their respective pairfed and control groups. Thus zinc deficiency state reduces zinc and MT concentrations in luminal fluid of epididymis and serum. 相似文献
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