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111.
Khurshid I. Molvi Vasudevan Sudarsanam Madhubhai M. Patel Navedul Haque 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):819-828
A new series of tetrasubstituted thiophene analogues (4a-4f, 5a-5f and 8a-8i) were designed incorporating the pharmacophoric features of COX-1 (as in fenamates), 5-LOX and the p38 MAP kinase inhibitors. The designed series was synthesized by nucleophilic addition of aryl/aroylisothiocyanate and enamine (2) yielding the addition product l-(α-Carbomethoxy-β-aminothiocrotonoyl)-aryl/aroyl amines (3/7); which on reaction with substituted phenacyl bromides gave the targeted tetrasubstituted thiophene esters (4a-4f / 8a-8i). The tetrasubstituted thiophenes esters (4a-4f ) on hydrolysis with one equivalent of potassium hydroxide solution in methanol at room temperature gave corresponding acids (5a-5f ). All the targeted compounds were evaluated for their anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at the doses of 10, 20 and 40 mg/kg body weight using standard drugs mefanamic acid and ibuprofen. The compounds (4c, 4e, 4f, 5f, 8a- 8i) which gave reasonable protection to the inflamed paw, eliciting good or moderate comparable anti-inflammatory activity were selected for investigating their analgesic activity using acetic acid induced writhing response test in albino mice at 10 mg/kg dose using standard drug ibuprofen and in order to arrive at possible mechanism of their anti-inflammatory activity, in vitro antioxidant nitric oxide radical scavenging assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 μg/mL were performed using standard drug ascorbic acid. 相似文献
112.
113.
Manoharan Rajesh Murugaraj Jeyaraj Ganeshan Sivanandhan Kondeti Subramanyam Thankaraj Salammal Mariashibu Subramanian Mayavan Gnanajothi Kapil Dev Vasudevan Ramesh Anbazhagan Markandan Manickavasagam Andy Ganapathi 《Plant Cell, Tissue and Organ Culture》2013,114(1):71-82
An efficient Agrobacterium-mediated genetic transformation method has been developed for the medicinal plant Podophyllum hexandrum Royle, an important source of the anticancer agent podophyllotoxin. Highly proliferating embryogenic cells were infected with Agrobacterium tumefaciens harbouring pCAMBIA 2301, which contains npt II and gusA as selection marker and reporter genes, respectively. The transformed somatic embryos and plantlets were selected on Murashige and Skoog (MS) basal medium containing kanamycin and germination medium, respectively. GUS histochemical analysis, polymerase chain reaction and Southern blot hybridisation confirmed that gusA was successfully integrated and expressed in the P. hexandrum genome. Compared with cefotaxime, 200 mg l?1 timentin completely arrested Agrobacterium growth and favoured somatic embryo development from embryogenic cells. Among the different Agrobacterium strains, acetosyringone concentrations and co-cultivation durations tested, embryogenic callus infected with A. tumefaciens EHA 105 and co-cultivated for 3 days on MS basal medium containing 100 μM acetosyringone proved to be optimal and produced a transformation efficiency of 29.64 % with respect to germinated GUS-positive plantlets. The Agrobacterium-mediated genetic transformation method developed in the present study facilitates the transference of desirable genes into P. hexandrum to improve the podophyllotoxin content and to enhance other useful traits. 相似文献
114.
115.
Kartik Sunagar Bryan Grieg Fry Timothy N. W. Jackson Nicholas R. Casewell Eivind A. B. Undheim Nicolas Vidal Syed A. Ali Glenn F. King Karthikeyan Vasudevan Vitor Vasconcelos Agostinho Antunes 《PloS one》2013,8(11)
Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation. 相似文献
116.
Kevin P. Cusack Hannes F. Koolman Udo E.W. Lange Hillary M. Peltier Isabel Piel Anil Vasudevan 《Bioorganic & medicinal chemistry letters》2013,23(20):5471-5483
Multiple technologies have emerged for structural diversification and efficient production of metabolites of drug molecules. These include expanded use of enzymatic and bioorganic transformations that mimic biological systems, biomimetic catalysis and electrochemical techniques. As this field continues to mature the breadth of transformations is growing beyond simple oxidative processes due in part to parallel development of more efficient catalytic methods for functionalization of unactivated scaffolds. These technologies allow for efficient structural diversification of both aromatic and aliphatic substrates in many cases via single step reactions without the use of protecting groups. 相似文献
117.
Anita Vasudevan 《The Yale journal of biology and medicine》2020,93(5):765
In medicine, we tend to think of food as being equivalent to nutrition, and food allergies are understood primarily as a biomedical process. In this piece, I explore how my experience with food allergies intersects with my cultural identity as a second-generation Indian-American. I also offer insights from my experiences in medical training and practice and reflect on the responsibility of health providers to understand the social and cultural context of food allergies. 相似文献
118.
The effects of explant and cytokinin types on in vitro plant regeneration of Ansellia africana were investigated. The exogenous addition of cytokinins is not required for the proliferation of new protocorms from Trimmed
protocorm cluster (TPC) explants. To the contrary, nodal and shoot-tip explants produced a single shoot in response to the
addition of cytokinins. Overall plant growth in terms of shoot length, leaf number, frequency of root organogenesis, root
length, and fresh weight/plant were significantly higher in media containing meta-Topolin Riboside (mTR) in both nodal and shoot-tip explants. Thidiazuron (TDZ) and 6-benzyladenine (BA) induced stunted and hypertrophied shoots
at their highest level (15 μM). In addition root differentiation and root growth were significantly lower on P668 media with
TDZ and BA. Zeatin was capable of inducing a significantly higher root organogenesis frequency and root length in TPC explants
as compared to other cytokinins. However, TPC explants produced a significantly greater number of longer shoots (>3 cm) on
P668 media with mTR. Hyperhydric shoots were produced from TPC explants. The occurrence of hyperhydricity is discussed with respect to the
culture vessel used in this study. 相似文献
119.
Panchapakesan G Dhayalan V Dhatchana Moorthy N Saranya N Mohanakrishnan AK 《Steroids》2011,76(13):1491-1504
Synthesis of various types of 2-(alkylaminomethyl) and 2-(aroyl) 17β-estradiol analogs are reported. The synthesis of similar types of 2-substituted 17-methylene estratriene analogs was also achieved. Synthesis of chalcone derivatives of 17β-estradiol and 17-methylene estratriene were also realized. All these 2-substituted estratrienes were tested for their antiproliferative activity by using four different cell lines from colon, lung, glioma and breast cancers. Among the various 2-substituted estratrienes, the compounds 10d, 14a-h and 17e were found to have in vitro antiproliferative activity comparable to that of parent analogs 1-4. Comparison of the SAR pattern of these 2-susbtituted estratriene derivatives confirmed that relatively, 17-methylene estratrienes are more active than that of 17β-estradiol analogs. 相似文献
120.
T Aoe I Huber C Vasudevan S C Watkins G Romero D Cassel V W Hsu 《The Journal of biological chemistry》1999,274(29):20545-20549
ADP-ribosylation factor 1 (ARF1) is a key regulator of transport in the secretory system. Like all small GTPases, deactivation of ARF1 requires a GTPase-activating protein (GAP) that promotes hydrolysis of GTP to GDP on ARF1. Structure-function analysis of a GAP for ARF1 revealed that its activity in vivo requires not only a domain that catalyzes hydrolysis of GTP on ARF1 but also a non-catalytic domain. In this study, we show that the non-catalytic domain of GAP is required for its recruitment from cytosol to membranes and that this domain mediates the interaction of GAP with the transmembrane KDEL receptor. Blocking its interaction with the KDEL receptor leaves the GAP cytosolic and prevents the deactivation in vivo of Golgi-localized ARF1. Thus, these findings suggest that the KDEL receptor plays a critical role in the function of GAP by regulating its recruitment from cytosol to membranes, where it can then act on its membrane-restricted target, the GTP-bound form of ARF1. 相似文献