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Pai, Aravinda
- Computational Approach for the Design of Novel Tankyrase Inhibitors:A Rational Study based on Pharmacophore and Atom based 3D QSAR
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Affiliations
1 Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences (MCOPS), Manipal University, Manipal, Karnataka, IN
2 Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences (MCOPS), Manipal University, Manipal, Karnataka, IN
3 Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences (MCOPS), Manipal University, Manipal, Karnataka, IN
1 Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences (MCOPS), Manipal University, Manipal, Karnataka, IN
2 Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences (MCOPS), Manipal University, Manipal, Karnataka, IN
3 Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences (MCOPS), Manipal University, Manipal, Karnataka, IN
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Research Journal of Pharmacy and Technology, Vol 10, No 3 (2017), Pagination: 778-784Abstract
Pharmacophore based screening was undertaken for a set of 30 flavones exhibiting Tankyrase I inhibitory activity. The two isoenzymes Tankyrase I and Tankyrase II share 80% sequence homology. This gives rise to the fine tuning required in the designing of small molecules wchich can selectively inhibit one or the other. In a recent study it was reported that, small molecule inhibitors of Tankyrases will be benificial in certain types of cancers like colorectal cancers. In future it may be a slective target for cancers like colorectal cancer. Four feature pharmacophores with one H bond acceptor and three aromatic rings were developped.The hypothesis ARRR2 was considered as best hypothesis ,which gave a statistically significant three dimensional QSAR model with corresponding statistical parameters (0.9028 as r2 value and 0.8548 as q2 value). The generated model was applied sucessfully on a set of both training and test set molecules. The squared corelation coefficient of 0.85 was observed between actual and predicted values in test set. The squared corelation coefficient of 0.96 was observed between actual and predicted value in training set. The built model will be useful in predicting the structural requirements needed for the selective inhibition of Tankyrase I.Keywords
Tankyrase, Pharmacophore, QSAR, Flavones.
- Computational Approach for the Design of Flavone based CDK2/CyclinA Inhibitors:A Simulation Study Employing Pharmacophore based 3D QSAR
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Authors
Affiliations
1 Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, IN
1 Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, IN
Source
Research Journal of Pharmacy and Technology, Vol 12, No 5 (2019), Pagination: 2299-2303Abstract
The present work aimed at designing selective and potent inhibitors of CDK2/CyclinA as anticancer agents. A five point pharmacophore (AAADR) model was developed for the reported molecules from literature, the pharmacophore model was used to build predictive 3D QSAR equation. The selected 3D QSAR models revealed the importance of hydrogen bond acceptors, hydrogen bond donors and aromatic rings for selectively towards the target enzyme. The developed models were statistically robust (CDK2/Cyclin A, Q2- 0.6380, R2 value of 0.9857, SD-0.1667, F-320.9 and Pearson coefficient value of 0.7916). The built model could be useful for the design and development of novel and selective inhibitors of CDK2/Cyclin A.Keywords
Flavopiridol, CDK, QSAR, Pharmacophore, GLIDE, Docking.References
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- L-Asparaginase from Soil actinomycetes:Optimization of Process Variables using Plackett Burman Method
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Authors
Affiliations
1 Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Udupi, Karnataka, IN
2 Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Udupi, Karnataka, IN
1 Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Udupi, Karnataka, IN
2 Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Udupi, Karnataka, IN
Source
Research Journal of Pharmacy and Technology, Vol 12, No 7 (2019), Pagination: 3487-3490Abstract
Extensive exploration of soil microorganisms in search of novel metabolites have edified researchers on the available natural products for drug discovery. Actinomycetes are filamentous Gram positive bacteria capable of producing wide array of bioactive metabolites. High GC content in the DNA, makes the organism unique and peculiar from other microorganisms. The present article contains data on purification and characterization of L-asparaginase from soil actinomycetes. Soil samples were collected from different locations in Udupi fish market, Karnataka, India. A total of 106 isolates were screened through rapid plate assay method, out of which 17 were found active. Furthermore, a promising isolate FMCL-13A with maximum enzyme activity was chosen by submerged fermentation technique. Statistical designs viz., Placket-Burman (PB) was employed for optimization of various experimental parameters in order to enhance L-asparaginase production. The nutritional variables which affects the enzyme production by submerged fermentation from the active isolate was optimized by PB model.Keywords
Actinomycetes, L-Asparaginase, Placket Burman Model, Optimization.References
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