Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targeting β-amyloid

Singh, Dev Bukhsh; Gupta, Manish Kumar; Kesharwani, Rajesh K.; Misra, Krishna

doi:10.1007/s13721-012-0021-7

Cited by 31 publications

(9 citation statements)

References 50 publications

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“…Fifteen principal descriptors as shown in Table 5 [34] and fourteen predicted ADME properties as shown in Table 6 were calculated for selected natural inhibitors by QikProp module of the Schrödinger software [35,36].…”

Section: Adme Descriptors Analysismentioning

confidence: 99%

Identification of Dual Natural Inhibitors for Chronic Myeloid Leukemia by Virtual Screening, Molecular Dynamics Simulation and ADMET Analysis

Kumar

Raj

Srivastava

et al. 2015

Interdiscip Sci Comput Life Sci

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Chronic myeloid leukemia (CML) is a disease of bone marrow stem cells caused by excessive growth and accumulation of granulocytes in the blood. Aberrant expression of the BCR-ABL proteins in bone marrow stem cells have found out in 95 % cases of CML. Tyrosine Kinase domains (SH2 and SH3) of BCR-ABL proteins are the potent targets to inhibit the process. Initially, imatinib is preferred as an efficient inhibitor to control functional activity of disease. Recently, it has been reported that the advanced stage of CML developed resistance against imatinib. In continuation, dasatinib is the first drug to combat against this disease by targeting multiple receptors and proven better as compared to imatinib. Here, an attempt has been made to identify similar analogs of dasatinib. Virtual screening was performed against various natural compound databases to get some potent natural compounds which are able to inhibit more than one receptor. Binding affinity of screened natural compounds was compared with some of the well-known inhibitors like imatinib, dasatinib, nilotinib etc., by analyzing their docking score and binding efficiency with the receptor. Stability of the best ligand-receptor complex was checked by performing 10 ns molecular dynamics simulation. ADMET properties of the obtained screened compounds were analyzed to check drug like property. Based on the aforementioned analysis, it has been suggested that these screened potent compounds are capable to inhibit multiple receptor proteins like ABL and SRC and consequently combat against the deadly disease CML.

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Section: Adme Descriptors Analysismentioning

confidence: 99%

Identification of Dual Natural Inhibitors for Chronic Myeloid Leukemia by Virtual Screening, Molecular Dynamics Simulation and ADMET Analysis

Kumar

Raj

Srivastava

et al. 2015

Interdiscip Sci Comput Life Sci

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“…Turmeric has broad range of medical applications against ulcer, inflammation, Alzheimer, malaria, liver cirrhosis, and skin disorders [3][4]. Therapeutic attributes of turmeric have been found mainly due to its polyphenolic ingredients collectively called as curcuminoids.…”

Section: Introductionmentioning

confidence: 99%

A Novel Approach for Overcoming Drug Resistance in Breast Cancer Chemotherapy by Targeting new Synthetic Curcumin Analogues Against Aldehyde Dehydrogenase 1 (ALDH1A1) and Glycogen Synthase Kinase-3 β (GSK-3β)

Kesharwani

Srivastava

Singh

et al. 2015

Appl Biochem Biotechnol

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Breast cancer stem cells are well known to resist the traditional methods like chemo and radio therapy. Aldehyde dehydrogenase 1 (ALDHIA1) and glycogen synthase kinase-3 β (GSK-3β) are the two selected proteins for study, due to their overexpression and upregulation in breast cancer cells. Curcumin, the yellow pigment of the spice turmeric, is widely reported as an antioxidant and acts as a synergist along with traditional drugs. Under hypoxic conditions, it gets converted to free radical which causes apoptosis. Three naturally occurring curcuminoids, i.e. curcumin, demethoxycurcumin, and bisdemethoxycurcumin along with five derivatives/analogues of curcumin, viz. 4,4'-di-O-(carboxy-methyl)-curcumin, 4-O-(2-hydroxyethyl)curcumin, 4,4'-di-O-allyl-curcumin, 4,4'-di-O-(acetyl)-curcumin, and 3,3'-bisdemethylcurcumin were synthesized and evaluated for their anti-breast cancer potential by docking simulation and assessment of their antioxidant character, studied via 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(·+)) radical cation scavenging assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical, and ferric reducing ability potential (FRAP) assay. A co-relation between structure and activity of curcuminoids/its analogues and derivatives has been worked out.

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“…The integrated pathways are useful to understand the evolution of disorder, off target and mode of action of drugs as well as in development of new therapeutic drugs (Kell 2006;Singh et al 2013). It is significant to identify the key properties and parameters which are used to predict the model.…”

Section: Introductionmentioning

confidence: 99%

Modeling and simulation analysis of propyl-thiouracil (PTU), an anti-thyroid drug on thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR), and sodium iodide (NIS) symporter based on systems biology approach

Gupta

Misra

2013

Netw Model Anal Health Inform Bioinforma

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The aim of metabolic modeling was to understand the cause effect interaction and reliance linked with the complex interactions of biological networks and molecular systems. Drugs that therapeutically modulate the biological processes of disease are often developed with limited knowledge of the underlying complexity of their specific targets. The robustness for systemic modulating behavior of thyroid hormone secretion during the course of different time unit simulation is explained in this study. In this work, a computational model has been developed which mimics the in vivo simulation. The model was constructed with the help of cell designer 4.1 used for analyzing the effect of perturbed amount of drugs at 0.1, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 amounts as a unit, targeting Thyroid Peroxidase (TPO), Thyroid Stimulating Hormone Receptor (TSHR), and Sodium Iodide Symporter (NIS). The rate kinetic equations were defined with each reaction to simulate the molecular species dynamic behavior. The modulating behavior of thyroid hormone secretion was analyzed by the process of activation and inactivation states of TPO, TSHR, and NIS at various amounts of drugs.Obtained results explain suitably the entire observable fact of the drug effects and are capable to proceed in response to the perturbations of the natural cell. TSHR was found as the most potent molecular therapeutic target in this study.

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Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targeting β-amyloid

Cited by 31 publications

References 50 publications

Identification of Dual Natural Inhibitors for Chronic Myeloid Leukemia by Virtual Screening, Molecular Dynamics Simulation and ADMET Analysis

Identification of Dual Natural Inhibitors for Chronic Myeloid Leukemia by Virtual Screening, Molecular Dynamics Simulation and ADMET Analysis

A Novel Approach for Overcoming Drug Resistance in Breast Cancer Chemotherapy by Targeting new Synthetic Curcumin Analogues Against Aldehyde Dehydrogenase 1 (ALDH1A1) and Glycogen Synthase Kinase-3 β (GSK-3β)

Modeling and simulation analysis of propyl-thiouracil (PTU), an anti-thyroid drug on thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR), and sodium iodide (NIS) symporter based on systems biology approach

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