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51.
Palani Kirubakaran Karthikeyan Muthusamy Kh. Dhanachandra Singh Selvaraman Nagamani 《Medicinal chemistry research》2013,22(8):3812-3822
The 3-phosphoinositide-dependent protein kinase-1 (PDK1) is an imminent target for discovering novel anticancer drugs. In order to understand the structure–activity correlation of naphthyridine-based PDK-1 inhibitors, we have carried out a combined pharmacophore, three-dimensional quantitative structure–activity relationship (3D-QSAR), and molecular docking studies. The study has resulted in six point pharmacophore models with four hydrogen bond acceptors (A), one hydrogen bond donor (D), and one aromatic ring (R) are used to derive a predictive atom-based 3D-QSAR model. The generated 3D-QSAR model shows that the alignment has good correlation coefficient for the training set compounds which comprises the values of R 2 = 0.96, SD = 0.2, and F = 198.2. Test set compounds shows Q 2 = 0.84, RMSE = 0.56, and Pearson-R = 0.84. The external validation was carried out to validate the predicted QSAR model which shows good predictive power of $ r_{m}^{2} $ = 0.83 and k = 1.01, respectively. The external validation results also confirm the fitness of the model. The results indicated that, atom-based 3D-QSAR models and further modifications in PDK1 inhibitors via pharmacophore hypothesis are rational for the prediction of the activity of new inhibitors in prospect of drug design. 相似文献
52.
Joji Kurian Thomas Min-Sik Kim Lavanya Balakrishnan Vishalakshi Nanjappa Rajesh Raju Arivusudar Marimuthu Aneesha Radhakrishnan Babylakshmi Muthusamy Aafaque Ahmad Khan Sruthi Sakamuri Shantal Gupta Tankala Mukul Singal Bipin Nair Ravi Sirdeshmukh Aditi Chatterjee T S Keshava Prasad Anirban Maitra Harsha Gowda Ralph H Hruban Akhilesh Pandey 《Cancer biology & therapy》2014,15(8):963-967
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Sripriya R Kumar MS Sehgal PK 《Journal of biomedical materials research. Part B, Applied biomaterials》2004,70(2):389-396
A novel bilayer dressing has been developed from bovine succinylated collagen. The dressing contains an antibiotic, Ciprofloxacin, for both immediate and time-regulated release for controlling the infection, as the infected open wounds need special care. The dressing consists of a sponge and a film, both prepared from succinylated bovine collagen. The sponge has a smooth surface on one side; its rough surface on the other side forms the bilayer system with the film. Both sponge and film act as an anionic reservoir to hold the cationic Ciprofloxacin. The drug, after dispersing in poly (N-vinyl-2-pyrrolidione) (PVP) solution is allowed to spread in the bilayer system by diffusion. The drug stays in the bilayer system because of ionic binding, but starts releasing when comes in contact with the wound. Release of the drug is immediate, but it is regulated by ionic binding between the drug and succinylated collagen. The wound exudates, and there is a polarity-controlled release of the drug from the bilayer system. The PVP and bilayer system permits only time-regulated release, and the system lasts up to 5 days with therapeutically sufficient drug availability. 相似文献
55.
Ganapathy V Thangaraju M Gopal E Martin PM Itagaki S Miyauchi S Prasad PD 《The AAPS journal》2008,10(1):193-199
SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na(+)-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and Müller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and gamma-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport. 相似文献
56.
Liu X Thangavel M Sun SQ Kaminsky J Mahautmr P Stitham J Hwa J Ostrom RS 《Naunyn-Schmiedeberg's archives of pharmacology》2008,377(4-6):359-369
Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor beta and inhibited by agents that elevate 3',5'-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this colocalization was functionally relevant. We found that cardiac fibroblasts produce cAMP in response to agonists for beta-adrenergic (isoproterenol), prostaglandin EP(2) (butaprost), adenosine (adenosine-5'-N-ethylcarboxamide, NECA), and prostacyclin (beraprost) receptors. Overexpression of AC6 increased cAMP production stimulated by isoproterenol and beraprost but not by butaprost or NECA. A key function of fibroblasts is the production of collagen. Isoproterenol- and beraprostmediated inhibition of collagen synthesis was also enhanced by AC6 overexpression, while inhibition by butaprost and NECA were unaltered. Lipid raft fractions from cardiac fibroblasts contain the preponderance of beta-adrenergic receptors and AC6 but exclude EP(2) receptors. While we could not determine the localization of native prostacyclin receptors, we were able to determine that epitope-tagged prostanoid IP receptors (IPR) expressed in COS7 cells did localize, in part, in lipid raft fractions. These findings indicate that IP receptors are expressed in lipid rafts and can activate raft-localized AC isoforms. AC6 is completely compartmentized in lipid raft domains where it is activated solely by coresident G protein-coupled receptors to regulate cardiac fibroblast function. 相似文献
57.
Anuradha Rajamanickam Nathella Pavan Kumar Arul Nancy P Nandhini Selvaraj Saravanan Munisankar Rachel Mariam Renji Vijayalakshmi V. Manoj Murhekar Jeromie Wesley Vivian Thangaraj Muthusamy Santhosh Kumar C. P. Girish Kumar Tarun Bhatnagar Manickam Ponnaiah R. Sabarinathan V. Saravana Kumar Subash Babu 《The American journal of tropical medicine and hygiene》2021,105(5):1255
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The past decade has led to marked improvements in our understanding regarding the pathogenesis and risk of progression of Barrett's esophagus (BE), enhanced imaging technology to improve dysplasia detection, and the development and refinement of endoscopic techniques, such as mucosal ablation and endoscopic mucosal resection(EMR), to eradicate BE. However, many questions remain including identifying which, if any, candidates are most appropriate for screening for BE; how to improve current surveillance protocols; predicting which patients with BE will develop neoplastic progression; identifying the most appropriate candidates for endoscopic eradication therapy; developing algorithms for appropriate management posteradication; and understanding the potential role of chemoprophylaxis. This article describes potential future advances regarding screening, surveillance, risk stratification, endoscopic eradication therapies, and chemoprevention and provides a potential future management strategy for patients with BE. 相似文献