Analysis of Binding Properties of Phosphoinositide 3-kinase Through In silico Molecular Docking

Daisy, P.; Sasikala, R.; Ambika, A.

doi:10.4172/jpb.1000086

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…The protein-ligand interaction plays a significant role in determining the molecular mechanism, followed by the interaction of the drugs with the active site to induce the desired effect (Daisy et al, 2009). In this perspective, molecular docking techniques are more likely to provide biologically sound results when applied to difficult drug targets such as an enzyme or receptor protein (Savarino, 2007).…”

Section: Discussionmentioning

confidence: 99%

Role of cytokines and Jak3/Stat3 signaling in the 1,2-dimethylhydrazine dihydrochloride-induced rat model of colon carcinogenesis

Saini

Vaish

Sanyal

2013

European Journal of Cancer Prevention

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The molecular mechanisms by which colon cancer cells regulate the expression of various proinflammatory and anti-inflammatory cytokines and transcription factors resulting in tumor progression have not been well clarified. The present study thus explores the effect of cancer cell-derived cytokines and transcription factors on the chemoprevention of a rat model of early colon carcinogenesis. Elevated expression of proinflammatory cytokines [interleukin-1β (IL-1β), IL-2, interferon γ, and tumor necrosis factor-α] and the transcription factors [Janus kinase 3 (Jak3) and signal transducer and activator of transcription 3 (Stat3)] was found in the 1,2-dimethylhydrazine dihydrochloride (DMH) group; however, this elevated expression was reversed by the individual and combination treatment with piroxicam, a traditional nonsteroidal anti-inflammatory drug [inhibiting both cyclooxygenase-1 (COX-1) and COX-2] and c-phycocyanin, a cyanobacterium-derived biliprotein from Spirulina platensis (selective COX-2 inhibitor). In the DMH group, low expression of IL-4, an anti-inflammatory cytokine, was further observed with respect to the other groups. Expression of inducible nitric oxide synthase and nitric oxide/citrulline levels was also analyzed and was found to be elevated with DMH treatment. Increased apoptotic index and stimulated levels of Bcl-2-associated death promoter (Bad), a proapoptotic protein, were observed in piroxicam-treated and c-phycocyanin-treated rats. In-silico molecular docking of piroxicam as a ligand with several regulatory proteins was performed, indicating that, except inducible nitric oxide synthase, it effectively binds with COX-1, COX-2, Jak3, and Stat3. Piroxicam and c-phycocyanin perhaps showed chemopreventive properties by inhibiting proinflammatory cytokines and Jak3/Stat3 signaling while promoting apoptosis. In addition, a combination regimen was found to be more beneficial than monotherapy.

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Section: Discussionmentioning

confidence: 99%

Role of cytokines and Jak3/Stat3 signaling in the 1,2-dimethylhydrazine dihydrochloride-induced rat model of colon carcinogenesis

Saini

Vaish

Sanyal

2013

European Journal of Cancer Prevention

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“…A number of powerful software programs, e.g. AutoDock [70,71], HEX [72,73], GOLD [74,75], FlexX, DOCK, Glide, Surflex, LigandFit, have been developed over the past several decades to carry out docking calculations, and good success in both binding mode and binding affinity prediction has often been achieved in selected test cases [76].…”

Section: Dockingmentioning

confidence: 99%

Computational Methods for Protein Structure Prediction and Its Application in Drug Design

Toomula¹

2011

J Bacteriol Parasitol

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Drug design and drug discovery are of critical importance in human health care. Computational approaches have become a major part of structure based drug design. Structure-based drug design utilizes the three dimensional structure of a protein target to design candidate drugs that are predicted to bind with high affinity and selectivity to the target. In this review computational methods for prediction of the protein structure are described and their use towards the drug design is discussed.

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“…It lacks p85 binding domain. This enzyme is further divided into p110γ catalytic unit and p101γ regulatory subunit [6]. The regulatory subunit of p110γ is responsible for the activation of the catalytic subunit downstream of G-proteins, of the protein complex to the membrane surface, where its lipid substrates are located [7][8].…”

Section: Class I Bmentioning

confidence: 99%

Insilico Receptor and Ligand Based Approach for Identifying the R Groups of Selected Pi3k Scaffold

Shrivastava¹,

Kumar²,

Prasad³

et al. 2016

EJB

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The scaffold hopping is an important process in Computer Aided Drug Designing (CADD).We have described an insilico methodology for selecting R groups through various receptor and ligand based approaches. This approach has been discussed in this article for PI3K scaffold of 4-thieno [3, 2-d] pyrimidin-4-ylmorpholine. The selected R groups were further ranked on the basis of interaction energy. The interaction energy results were further compared with IC50 values reported in literature.The present studies will throw light on the selection of various R groups at Insilico level without synthesis and invitro studies at initial phase of drug designing. This approach will be helpful in resource optimization during drug discovery.

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Analysis of Binding Properties of Phosphoinositide 3-kinase Through In silico Molecular Docking

Cited by 9 publications

References 40 publications

Role of cytokines and Jak3/Stat3 signaling in the 1,2-dimethylhydrazine dihydrochloride-induced rat model of colon carcinogenesis

Role of cytokines and Jak3/Stat3 signaling in the 1,2-dimethylhydrazine dihydrochloride-induced rat model of colon carcinogenesis

Computational Methods for Protein Structure Prediction and Its Application in Drug Design

Insilico Receptor and Ligand Based Approach for Identifying the R Groups of Selected Pi3k Scaffold

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