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Siddheshwar K. Chauthe Sandip B. Bharate Sudeep Sabde Debashis Mitra Kamlesh K. Bhutani Inder P. Singh 《Bioorganic & medicinal chemistry》2010,18(5):2029-2036
Plants are an important source of a variety of bioactive compounds with different modes of action. Anti-HIV agents from plant sources can be useful in developing novel therapies for inhibiting HIV infection. Based on the reported anti-HIV activity of plant derived phloroglucinols, several new dimeric phloroglucinols were synthesized in the present study by varying substitution on aromatic ring and at methylene bridge. Some of the synthesized compounds have shown good HIV inhibitory activity in a human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL4.3 virus isolate. Structure–activity studies indicate that phenyl, 4-benzyloxy-1-phenyl and cyclohexyl substitution at methylene bridge gave compounds with better anti-HIV activity. Compounds 22 and 24 showed highest anti-HIV activity with an IC50 of 0.28 μM and 2.71 μM, respectively, former was more active than the positive standard AZT in cell based assay. 相似文献
34.
Kamlesh K. Gupta Aranda R. Slabbekoorn Benjamin A. Paulson Holly V. Goodson 《Journal of molecular biology》2010,395(5):1049-774
Cytoplasmic linker protein 170 (CLIP-170) is a microtubule (MT) plus-end tracking protein (+ TIP) that dynamically localizes to the MT plus end and regulates MT dynamics. The mechanisms of these activities remain unclear because the CLIP-170-MT interaction is poorly understood, and even less is known about how CLIP-170 and other + TIPs act together as a network. CLIP-170 binds to the acidic C-terminal tail of α-tubulin. However, the observation that CLIP-170 has two CAP-Gly (cytoskeleton-associated protein glycine-rich) motifs and multiple serine-rich regions suggests that a single CLIP-170 molecule has multiple tubulin binding sites, and that these sites might bind to multiple parts of the tubulin dimer. Using a combination of chemical cross-linking and mass spectrometry, we find that CLIP-170 binds to both α-tubulin and β-tubulin, and that binding is not limited to the acidic C-terminal tails. We provide evidence that these additional binding sites include the H12 helices of both α-tubulin and β-tubulin and are significant for CLIP-170 activity. Previous work has shown that CLIP-170 binds to end-binding protein 1 (EB1) via the EB1 C-terminus, which mimics the acidic C-terminal tail of tubulin. We find that CLIP-170 can utilize its multiple tubulin binding sites to bind to EB1 and MT simultaneously. These observations help to explain how CLIP-170 can nucleate MTs and alter MT dynamics, and they contribute to understanding the significance and properties of the + TIP network. 相似文献
35.
Kaur A Singh R Dey CS Sharma SS Bhutani KK Singh IP 《Indian journal of experimental biology》2010,48(3):314-317
Hexane, chloroform and ethyl acetate extracts (100 microg/ml) of Alpinia galanga rhizomes exhibited significant activity in vitro against promastigotes of L. donovani. Twelve compounds namely, methyleugenol (1), p-coumaryl diacetate (2), 1'-acetoxychavicol acetate (3), 1'-acetoxyeugenol acetate (4), trans-p-acetoxycinnamyl alcohol (5), trans-3,4-dimethoxycinnamyl alcohol (6), p-hydroxybenzaldehyde (7), p-hydroxycinnamaldehyde (8), trans-p-coumaryl alcohol (9), galangin (10), trans-p-coumaric acid (11) and galanganol B (12) were isolated from these extracts. Of these, compounds 2, 3, 4 and 5 were found most active in vitro against promastigotes of L. donovani with IC50 values of 39.3, 32.9, 18.9 and 79.9 microM respectively. This is the first report of antileishmanial activity of the extracts and isolated constituents of A. galanga. 相似文献
36.
Gohil VM Agrawal SK Saxena AK Garg D Gopimohan C Bhutani KK 《Indian journal of experimental biology》2010,48(3):265-268
Aryl hydrazine and hydrazide analogues were synthesized based on p-tolyl hydrazine, isolated as a breakdown product of a secondary metabolite from the mushroom, Agaricus bisporus, and tested to be highly active molecule than 5-fluorouracil in in vitro anticancer studies. The synthesized analogues were tested for anticancer activity using NCI protocol. Anolgues 12 and 15 emerged as molecules with significant in vitro anticancer activity. Molecular docking study revealed the binding orientations of aryl hydrazines and hydrazides analogues in the active sites of thymidylate synthase. 相似文献
37.
Cellular information processing requires the coordinated activity of a large network of intracellular signalling pathways. Cross-talk between pathways provides for complex non-linear responses to combinations of stimuli, but little is known about the density of these interactions in any specific cell. Here, we have analysed a large-scale survey of pathway interactions carried out by the Alliance for Cellular Signalling (AfCS) in RAW 264.7 macrophages. Twenty-two receptor-specific ligands were studied, both alone and in all pairwise combinations, for Ca2+ mobilization, cAMP synthesis, phosphorylation of many signalling proteins and for cytokine production. A large number of non-additive interactions are evident that are consistent with known mechanisms of cross-talk between pathways, but many novel interactions are also revealed. A global analysis of cross-talk suggests that many external stimuli converge on a relatively small number of interaction mechanisms to provide for context-dependent signalling. 相似文献
38.
Gohil VM Brahmbhatt KG Loiseau PM Bhutani KK 《Bioorganic & medicinal chemistry letters》2012,22(12):3905-3907
β-carbolines from various natural and synthetic sources have been known to show diverse biological activities. As a part of our current ongoing project to search for potent natural product-derived anti-leishmanial compounds, we have synthesized a series of substituted 1-aryl-β-carboline derivatives. A total of 22 compounds were synthesized and tested in vitro against Leishmania donovani, out of which 6 compounds (4, 5, 10, 11, 19 and 22) showed notably more activity than the standard miltefosine (IC(50) 12.07±0.82 μM), with compound 4 being the most potent (IC(50) 2.16±0.26 μM). 相似文献
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Kamlesh R. Chauhan 《Biocontrol Science and Technology》2008,18(7):727-731
Field-collected female goldeneyed lacewing (Chrysopa oculata) strongly avoided ovipositing on substrates exposed over 24 h to three of four lady beetle species tested, resulting in circa 3-fold higher egg deposition on control versus coccinellid-exposed substrates. The effect was stage-specific for Coleomegilla maculata; it was observed for adult and third-instar larvae but not for unfed first-instar larvae. 相似文献