Molecular docking analysis of curcumin analogues against kinase domain of ALK5

Kandagalla, Shivananda; Sharath, B S; Bharath, Basavapattana Rudresh; Hani, Umme; Hanumanthappa, M.

doi:10.1007/s40203-017-0034-0

Cited by 32 publications

(18 citation statements)

References 45 publications

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“…PreADMET reveals that investigated COs are not inhibitors of the P-glycoprotein and outcomes values for the blood brain barrier penetration that are lower than 0.1 that correspond to a low absorbance to central nervous system (Aswathy et al, 2018). The PPB binding assessment (percentage of drug bound in plasma protein) reveals that investigated COs exhibit low binding energy with plasma proteins (PPB<90%) (Kandagalla et al, 2017) with the exception of the oligomer 6D that shows a high binding energy to plasma proteins (93.384%). SwissADME predicts that investigated compounds are not able to penetrate the blood brain barrier and are considered as substrates of P-glycoprotein.…”

Section: Resultsmentioning

confidence: 99%

“…The action of chemicals depends on their interactions with plasma proteins, with unbound molecules usually reflecting better interactions with their targets and influencing the efficacy of the molecules (Kandagalla et al, 2017). All computational facilities that we have used reveal that COs considered in this study exhibit low potential to bind to plasma proteins.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Roman

Som

et al. 2019

Front. Bioeng. Biotechnol.

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Chitosan is a natural polymer revealing an increased potential to be used in different biomedical applications, including drug delivery systems, and tissue engineering. It implies the evaluation of the organism response to the biomaterial implantation. Low-molecular degradation products, the chito-oligomers, are resulting mainly from the influence of enzymes, which are found in the organism fluids. Within this study, we have performed the computational assessment of pharmacological profiles and toxicological effects on human health of small chito-oligomers with distinct molecular weights, deacetylation degrees, and acetylation patterns. Our approach is based on the fact that regulatory agencies and researchers in the drug development field rely on the use of modeling to predict biological effects and to guide decision making. To be considered as valid for regulatory purposes, every model that is used for predictions should be associated with a defined toxicological endpoint and has appropriate robustness and predictivity. Within this context, we have used FAF-Drugs4, SwissADME, and PreADMET tools to predict the oral bioavailability of chito-oligomers and SwissADME, PreADMET, and admetSAR2.0 tools to predict their pharmacokinetic profiles. The organs and genomic toxicities have been assessed using admetSAR2.0 and PreADMET tools but specific computational facilities have been also used for predicting different toxicological endpoints: Pred-Skin for skin sensitization, CarcinoPred-EL for carcinogenicity, Pred-hERG for cardiotoxicity, ENDOCRINE DISRUPTOME for endocrine disruption potential and Toxtree for carcinogenicity and mutagenicity. Our computational assessment showed that investigated chito-oligomers reflect promising pharmacological profiles and limited toxicological effects on humans, regardless of molecular weight, deacetylation degree, and acetylation pattern. According to our results, there is a possible inhibition of the organic anion transporting peptides OATP1B1 and/or OATP1B3, a weak potential of cardiotoxicity, a minor probability of affecting the androgen receptor, and phospholipidosis. Consequently, these results may be used to guide or to complement the existing in vitro and in vivo toxicity tests, to optimize biomaterials properties and to contribute to the selection of prototypes for nanocarriers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Roman

Som

et al. 2019

Front. Bioeng. Biotechnol.

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“…In addition to TGF-β signaling pathway, curcumin is able to suppress receptors in this pathway. Curcumin and its derivatives inhibit ALK5 to down-regulate migration and invasion of cancer cells ( Kandagalla et al, 2017 ).…”

Section: Curcumin and Transforming Growth Factor-beta In Different DImentioning

confidence: 99%

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

et al. 2020

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Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

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“…The lowest binding energy results were considered for further postdocking analysis. 55 The top-possible 5 phytoconstituents with the best docking score of Aβ and AChE were screened further for their drug-likeness through the admetSAR prediction, which revealed that 2 out of the 5 compounds tested for Aβ target; that is, 1-heneicosanol and N-nonadecanol-1. These compounds do not have carcinogenicity and have better BBB permeation, intestinal absorption, and less oral toxicity.…”

Section: Discussionmentioning

confidence: 99%

In Silico Molecular Docking Analysis of Potential Anti-Alzheimer's Compounds Present in Chloroform Extract of Carissa carandas Leaf Using Gas Chromatography MS/MS

Kareti

Subash

2020

Current Therapeutic Research

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Background: The current treatment of Alzheimer's disease (AD) is far from adequate. AD can be treated by inhibiting either β-amyloid protein deposition or acetylcholinesterase enzyme activity. Many treatments for AD are directed at these 2 targets. In the present study, the phytoconstituents of Carissa carandas chloroform leaf extract were identified by gas chromatography-MS/MS analysis, and in silico molecular docking studies were performed to evaluate their potential against AD. Objectives: The present study aimed to identify the possible anti-Alzheimer's activity of novel phytoconstituents isolated from C carandas . Methods: The powdered leafy material was subjected to successive Soxhlet extraction using 3 different solvents: n-hexane, chloroform, and methanol. The chloroform extract was subjected to gas chromatography-MS/MS analysis, and the observed chromatogram revealed the presence of 48 chemical constituents. Among them, 42 new phytoconstituents are reported in this plant for the first time. The gas chromatography-MS/MS–identified phytoconstituents were evaluated by iGEMDOCK software against AD targets of β-amyloid fibril (protein data bank ID: 2LMN) and recombinant human acetylcholinesterase (protein data bank ID: 3LII) ligands, and their anti-AD potential were compared with those of known inhibitors of galantamine and curcumin. Results: On the basis of results from both docking assays, the 5 compounds with the highest docking energy were further analyzed using in silico admetSAR web portal modeling for the evaluation of parameters such as intestinal absorption, blood-brain barrier permeation, carcinogenicity, and acute oral toxicity. Conclusions: The chloroform leaf extract of C carandas was found to contain constituents that have affinities for the 2 targets tested; that is, amyloid β and acetylcholinesterase. The best docking scores were found for 7 compounds: 1-heneicosanol; N-nonadecanol-1; cholesta-4,6-dien-3-ol, (3beta); di-n-octyl phthalate; 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione; 6-undecyl-5,6-dihydro-2H-pyran-2-one, and phenol, 2,4-di-t-butyl-6-nitro compounds, and these compounds were therefore suggested to be promising anti-AD lead compounds. Further, the target leads were subjected to ligplot analysis for their 2-dimensional representation of hydrogen bonding and hydrophobic interactions. Thus, the results obtained from the in silico study of C carandas leaf extract using these computational approaches indicate the presence of phytoconstituents that have affinities for the selected 2 targets of AD. ( Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)

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Molecular docking analysis of curcumin analogues against kinase domain of ALK5

Cited by 32 publications

References 45 publications

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

In Silico Molecular Docking Analysis of Potential Anti-Alzheimer's Compounds Present in Chloroform Extract of Carissa carandas Leaf Using Gas Chromatography MS/MS

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