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Vishnu Prasanth Vinukonda, Srinivas Kumar Palakeerti, Blessy Christina Nalakurthi, John Dogulas Palleti*
International Journal of Bioassays , 2012,
Abstract: Protein-ligand docking analysis was carried out using AutoDock Vina on 61 compounds from two different plants, Justicia adhatoda and Ocimum sanctum with FtsZ protein of Mycobacterium tuberculosis. Various experimentally tested FtsZ inhibitors from literature were also studied before screening plant based compounds. The average dock score of the inhibitors taken from the literature was 7.2kcal/mol. After docking 61 compounds from two different plants, a final set of compounds were selected by filtering compounds that showed dock scores greater than 7.0kcal/mol. Following this criteria, 10 compounds each from Justicia adhatoda and Ocimum sanctum were finalized. In the next step, consensus scoring was employed to study the importance of various scoring functions available in other docking software’s such as Molegro, GOLD, Patch dock and MEDock respectively. From the scoring generated based on rank-sum technique, Anisotine, Betasitosterol Beta-D glucoside, Lyoniside from Justicia adhatoda, Rosmarinic acid, Stigmasterol, Ursolic acid from Ocimum sanctum were found to be the best inhibitors of FtsZ protein.
Molecular Modeling Study of 2-Substituted Isoindoline Derivatives of α-Amino Acids as Inhibitors of Lipoxygenase by Docking Simulations
Mancilla Percino, Teresa;Correa Basurto, José;Alavés Carbajal, Karla S.;Valle-Sandoval, Nagchielli;Trujillo Ferrara, José;
Journal of the Mexican Chemical Society , 2009,
Abstract: in this work two series of isoindolines 1(a-g) and 2(a-g) were evaluated as possible inhibitors of lipoxygenase (lox) by docking studies, as well as for the antiinflammatories isoindolilamides 3-5 and ibuprofen 6, as part of a theoretical study to found dual lox/ cox inhibitory activities. therefore, dihydrodimethylbenzofurane 7, licofelone 8 and darbufelone 9 were also evaluated, which are well-known as dual lox/cox inhibitors and consequently, in this work they were used to identify their binding sites on the lox and compared with those obtained from 1(a-g), 2(a-g) and 3 to 6 under study. analysis of the results showed that all compounds under study could inhibit to the lox, since they are binding in the same or close to the region as the compounds 7-9 taken as references. several interactions of heteroatom of all compounds with the amino acid residues of binding sites of lox were determined. the δg values were obtained for all the complexes (lox-compound), among all the complexes, lox-8 (-12.76 kcal/mol) resulted to be the most stable; and from the compounds under study, lox-1f (-8.97 kcal/mol) resulted to be more stable than the other compounds tested. whereas, theoretical dissociation constant values kd (μm) were obtained. among all compounds, 8 (0.000433 μm) showed more affinity to lox; while from compounds under study, 1f (0.266 μm) exhibited more affinity to lox. these results also show that compounds 1(a-g) and 2(a-g), and 3-6 could have a dual lox/cox/ inhibition, as have been shown for 7-9 and from their similar docking study within the cox-1 and cox-2 previously reported.
Docking of phosphonate and trehalose analog inhibitors into M. tuberculosis mycolyltransferase Ag85C: Comparison of the two scoring fitness functions GoldScore and ChemScore, in the GOLD software  [cached]
Manoj Kumar Annamala,Krishna Kishore Inampudi,Lalitha Guruprasad
Bioinformation , 2007,
Abstract: The Ag85 family enzymes are responsible for the synthesis of cell wall components in mycobacterial species. Inhibitors to these enzymes are potential antimycobacterial agents. We have carried out the docking of phoshonate and trehalose analog inhibitors into the three dimensional structure of mycolyltransferase enzyme, Ag85C of M. tuberculosis using the GOLD software. The inhibitor binding positions and affinity were evaluated using both the scoring fitness functions- GoldScore and ChemScore. We observed that the inhibitor binding position identified using the GoldScore was marginally better than the ChemScore. A qualitative agreement between the reported experimental biological activities (IC50) and the GoldScore was observed. We identified that amino acid residues Arg541, Trp762 are important for inhibitor recognition via hydrogen bonding interactions. This information can be exploited to design Ag85C specific inhibitors.
Comparative molecular docking analysis of essential oil constituents as elastase inhibitors  [cached]
Periyasamy Sivamani,Ganesan Singaravelu,Venkatesan Thiagarajan,Tamilarasu Jayalakshmi
Bioinformation , 2012,
Abstract: Elastase is a protease or proteolytic enzyme, responsible for the breakdown of protein. There are eight human genes encoding for elastase, of which Elastase-1 (CELA-1) and Elastase-2 (ELANE) has significant implications on human diseases. Elastase-1 is primarily expressed in skin keratinocytes and is regarded as the major cause for the blistering in bullous pemphigoid, which affects the skin. On the other hand, Elastase-2 (ELANE), is expressed in the azurophil granules of neutrophils, is responsible for pulmonary emphysema and cyclic hematopoiesis a rare genetic disorder. Elastase is also produced by bacteria such as Pseudomonas aeruginosa, and forms the virulent factor in human. The ingredients from essential natural oils were found to have wound healing effects on non-healing wounds that is interfered by elastase due to microbial infection. Essential oils such as citral, citronellal, geranial, geraniol, and thymol were screened for their inhibitory activity on elastase produced by neutrophil, skin, and Pseudomonas aeruginosa by docking and were analyzed for their subcutaneous ADMET properties by ADME – TOX – Web server
Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study  [PDF]
Mehran Fadaeinasab,A. Hamid A. Hadi,Yalda Kia,Alireza Basiri,Vikneswaran Murugaiyah
Molecules , 2013, DOI: 10.3390/molecules18043779
Abstract: Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC 50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: ( E)-3-(3,4,5-trimethoxyphenyl)acrylic acid ( 1), ( E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate ( 2), 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate ( 3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline ( 4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC 50 = 60.17 μM) and BChE (IC 50 = 61.72 μM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.
Proteomic analysis of streptomycin resistant and sensitive clinical isolates of Mycobacterium tuberculosis
Prashant Sharma, Bhavnesh Kumar, Yash Gupta, Neelja Singhal, Vishwa Katoch, Krishnamurthy Venkatesan, Deepa Bisht
Proteome Science , 2010, DOI: 10.1186/1477-5956-8-59
Abstract: Two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was employed for analyzing the protein profiles. Homology and in silico characterization for identified proteins was assessed using BLAST, InterProScan and KEGG database searches. Computational studies on the possible interactions between SM and identified proteins were carried out by a battery of online servers and softwares, namely, CLUSTALW (KEGG), I-TASSER, VMD, PatchDock and FireDock. On comparing 2DE patterns, nine proteins were found consistently overexpressed in SM resistant isolates and were identified as Rv0350, Rv0440, Rv1240, Rv3075c, Rv2971, Rv3028c, Rv2145c, Rv2031c and Rv0569. In silico docking analysis showed significant interactions of SM with essential (Rv0350, Rv0440 and Rv2971) and non essential (Rv1240, Rv3075c and Rv2031c) genes.The computational results suggest high protein binding affinity of SM and suggested many possible interactions between identified proteins and the drug. Bioinformatic analysis proves attributive for analysis of diversity of proteins identified by whole proteome analysis. In-depth study of the these proteins will give an insight into probable sites of drug action other than established primary sites and hence may help in search of novel chemotherapeutic agents at these new sites as inhibitors.Tuberculosis is one of the most challenging infectious diseases. Globally, 9.2 million new cases and 1.7 million deaths occur due to this disease [1]. Its impact on public health is further aggravated by co-infection with human immunodeficiency virus, emergence of multi-drug resistant strains and reactivation of the dormant bacteria. Attempt for primary prevention using Bacillus Calmette Guerin (BCG) and other integral vaccines have generally been disappointing though some subunit vaccines are under trial [2]. The excessive emergence of drug resistant tuberculosis has stimulated interest in the under
Molecular docking study of P4-Benzoxaborole-substituted ligands as inhibitors of HCV NS3/4A protease  [cached]
Abdul Wadood,Muhammad Riaz,Syed Babar Jamal,Masaud Shah
Bioinformation , 2013,
Abstract: NS3/4A protease is an important emerging target for the cure of hepatitis C. There are many inhibitors of HCV NS3/4A protease that are passing through the clinical improvement indicating momentous reduction in the viral infection rate of patients. In this study molecular docking via MOE-Dock program was used to evaluate binding interactions of ligands with HCV NS3/4A protease. The docking and experimental results were found in good correlation. The best conformations of ligands were analyzed for binding interactions with the residues of binding cavity of NS3/4A protease. The valuable binding interactions and docking scores were observed for compounds 01, 05, 06, 07, 08 and 09
Non-Intercalative Triterpenoid Inhibitors of Topoisomerase II: A Molecular Docking Study
William N. Setzer
The Open Bioactive Compounds Journal , 2009, DOI: 10.2174/1874847300801010013]
Abstract: Theoretical flexible docking studies were carried out on a number of triterpenoids previously shown to be inhibitors of topoisomerase II in order to assess the nature of binding of these non-intercalative inhibitors to the enzyme. The molecular docking results suggest that most of the triterpenoids preferentially bind to the DNA binding site of topoisomerase II, while a few also bind to the ATP binding site. These results provide some insight into the mode of activity of these cytotoxic natural products.
Molecular Docking of Aromatase Inhibitors  [PDF]
Naravut Suvannang,Chanin Nantasenamat,Chartchalerm Isarankura-Na-Ayudhya,Virapong Prachayasittikul
Molecules , 2011, DOI: 10.3390/molecules16053597
Abstract: Aromatase is an enzyme that plays a critical role in the development of estrogen receptor positive breast cancer. As aromatase catalyzes the aromatization of androstenedione to estrone, a naturally occurring estrogen, it is a promising drug target for therapeutic management. The undesirable effects found in aromatase inhibitors (AIs) that are in clinical use necessitate the discovery of novel AIs with higher selectivity, less toxicity and improving potency. In this study, we elucidate the binding mode of all three generations of AI drugs to the crystal structure of aromatase by means of molecular docking. It was demonstrated that the docking protocol could reliably reproduce the interaction of aromatase with its substrate with an RMSD of 1.350 ?. The docking study revealed that polar (D309, T310, S478 and M374), aromatic (F134, F221 and W224) and non-polar (A306, A307, V370, L372 and L477) residues were important for interacting with the AIs. The insights gained from the study herein have great potential for the design of novel AIs.
Gastrointestinal tuberculosis is not associated with proton pump inhibitors: A retrospective cohort study  [cached]
Kyoung Sup Hong,Seung Joo Kang,Jong Kyoung Choi,Ju Han Kim
World Journal of Gastroenterology , 2013, DOI: 10.3748/wjg.v19.i2.258
Abstract: AIM: To evaluate the effect of proton pump inhibitors (PPIs) on the development of gastrointestinal tuberculosis. METHODS: All patients who were more than 20 years old and who had received a prescription for PPIs among those who visited Seoul National University Hospital from January 1, 2005 to December 31, 2009 were identified. Due to the low sensitivity of the microbiologic test and the nonspecific pathologic findings, the diagnosis of gastrointestinal tuberculosis was confirmed through the presence of active ulcerations and the responses to anti-tuberculosis medications. The patients were divided into two groups according to treatment duration (group 1: ≤ 3 mo; group 2: > 3 mo) and were followed up from the time they took the first prescription of PPIs until their last visit. Logistic regression analysis was used to calculate the relative risks (RR) and 95%CI, adjusting for covariates. RESULTS: Among the 61 834 patients exposed to PPIs (50 534 in group 1; 11 300 in group 2), 21 patients were diagnosed with PPI-associated gastrointestinal tuberculosis during 124 274 person-years of follow-up. Of 21 patients, the 12 who revealed only scar changes in the colonoscopy were excluded from the statistical analyses. Of those who remained, 2 were excluded because they underwent gastrointestinal endoscopy within 4 wk of the first prescription for PPIs. Longer exposure to PPI was associated with a higher mean age (55.0 ± 14.5 in group 1 vs 58.2 ± 13.3 in group 2, P < 0.001) and a higher Charlson co-morbidity index (0.50 ± 0.93 in group 1 vs 0.77 ± 1.14 in group 2, P < 0.001). The true incidence of active gastrointestinal tuberculosis was 0.65 per 1000 person-years in group 1 and 0.03 per 1 000 person-years in group 2. Like the less-than-three-month PPI treatment period in group 1, the over-three-month PPI therapy period in group 2 was not associated with increased risk of acquiring gastrointestinal tuberculosis, after adjusting for age and co-morbidities, whereas the Charlson co-morbidity index was associated with increased risk of acquiring gastrointestinal tuberculosis based on the score [RR: (reference 1) in group 1 vs 1.518 in group 2; 95% CI: 1.040-2.216, P = 0.03]. CONCLUSION: Long-term PPI therapy does not seem to be associated with increased risk of acquiring gastrointestinal tuberculosis, but a higher Charlson co-morbidity index is associated with such.
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