Cancer comprises a group of diseases which are involved in the aberrant growth of the cells causing disruption of normal body function. Due to the lack of proper sophisticated treatments this nasty disease leads to th...Cancer comprises a group of diseases which are involved in the aberrant growth of the cells causing disruption of normal body function. Due to the lack of proper sophisticated treatments this nasty disease leads to the death of most of the patients affected with it. Moreover, treatments like chemotherapy involve other post-treatment complications which make them unfavorable for extended use. Medicinal plants possess many phytochemicals of great therapeutic value and many of them are effective in killing cancer cells. These compounds working by variety of mechanisms and in most of the cases exhibit their anticancer potentiality by inhibiting many proteins involved in cell growth and division. Molecular docking is a computational approach which facilitates the finding of the best molecule from a group which may bind with the highest affinity with the intended target by providing a virtual biological system. This process works on the basis of specific algorithm and involves scoring function to rank the molecules that fit with the target. This study has been designed to investigate the potentiality of four phytochemicals from Clitoria ternatea—Kaempferol, Myricetin, P-Hydroxycinnamic acid and Quercetin as inhibitors of two cell cycle checkpoint proteins—Cyclin Dependent Kinase-2 (CDK-2) and Cyclin Dependent Kinase-6 (CDK-6) in Cyclin/CDK pathway. Quercetin and Myricetin docked with higher affinity with CDK-2 and CDK-6 respectively. Drug likeness property analysis and ADME/T test impose computational approach to investigate physicochemical and pharmacological properties of candidate drug molecules. P-Hydroxycinnamic acid performed well in both drug likeness property analysis and ADME/T than Quercetin and Myricetin. So, P-Hydroxycinnamic acid is the best finding of this experiment.展开更多
This experiment has been carried out to observe the potential thrombolytic activity of naturally occuring phytochemicals in Ginger (Zingiber officinale) and to analyze their drug likeness property and ADME/T profile. ...This experiment has been carried out to observe the potential thrombolytic activity of naturally occuring phytochemicals in Ginger (Zingiber officinale) and to analyze their drug likeness property and ADME/T profile. Thrombolytic activity of Ginger has already been confirmed in laboratory experiment and this study focuses on the molecular interactions among four phytocompounds (Isovanillin, Gingerol, Beta-sitosterol and 2,6-Dimethyl-2-octene-1,8-diol) found in Ginger and Tissue Plasminogen Activator (tPA). Present experiment is largely based on computer-aided drug design protocol where the strength of interaction is described as binding energy function. Isovanillin exhibited better docking score, and so this compound might have greater thrombolytic activity than others. Moreover, Isovanillin also suggested sound drug likeness property and ADME/T profile which predicts its safeness for consumption in human body. But Beta-sitosterol violated Lipinski’s rule of five and 2, 6-Dimethyl-2-octene-1,8-diol showed the lowest affinity of binding with tPA. However, further in vivo or in vitro study may be required to confirm the thrombolytic activity of Isovanillin.展开更多
Alzheimer’s Disease (AD) is the most prevalent age-related dementia. AD can be caused by abnormal processing of amyloid precursor protein (APP) or by oxidative stress or may be due to the actions of kinases or the de...Alzheimer’s Disease (AD) is the most prevalent age-related dementia. AD can be caused by abnormal processing of amyloid precursor protein (APP) or by oxidative stress or may be due to the actions of kinases or the degeneration and loss of functions of neurons in the brain. Although various treatments have already gained success in the in vitro studies, however, till now not a single satisfactory drug has been proven that can cure this disease permanently till now. In this study, the best possible drug has been determined from a group of drug molecules using methods of molecular docking. Molecular docking is a computational approach which helps to determine the best molecule from a group of molecules which may bind with the highest affinity with the intended target by mimicking the original biological environment in a computer. The tested drug molecules in this experiment are the disease modifying agents, capable of inhibiting a particular protein involving in the AD pathway. Eight drug molecules (ligands)-memantine (-4.075 Kcal/mol), hymenialdisine (-8.079 Kcal/mol), tideglusib (-6.445 Kcal/mol), kenpaullone (-7.545 Kcal/mol), dihydrospiro[dibenzo[a,d][7]annulene-5,4’-imidazol] (-4.742 Kcal/mol), harmine (-7.57 Kcal/mol), harmol (-6.583 Kcal/mol) and 1-Methyl-4-Phenylpyridinium (-5.214 Kcal/mol), have been docked successfully against four targets (proteins)-N-Methyl-D-Aspartate Receptor (NMDAR), glycogen synthase kinase-3β (GSK-3β), beta-secretase (β-secretase) and dual specificity tyrosine (Y)-phosphorylation-regulated kinase 1A (DYR-K1A) in this experiment which are intended targets in current AD treatment approaches. Investigation of docking results, druglikeness properties and ADME/T testing results suggest that the best findings of this experiment are memantine, hymenialdisine, dihydrospiro[dibenzo[a,d][7]annulene-5,4’-imi- dazol] and harmol, that could be the best possible drugs for the treatment of AD.展开更多
文摘Cancer comprises a group of diseases which are involved in the aberrant growth of the cells causing disruption of normal body function. Due to the lack of proper sophisticated treatments this nasty disease leads to the death of most of the patients affected with it. Moreover, treatments like chemotherapy involve other post-treatment complications which make them unfavorable for extended use. Medicinal plants possess many phytochemicals of great therapeutic value and many of them are effective in killing cancer cells. These compounds working by variety of mechanisms and in most of the cases exhibit their anticancer potentiality by inhibiting many proteins involved in cell growth and division. Molecular docking is a computational approach which facilitates the finding of the best molecule from a group which may bind with the highest affinity with the intended target by providing a virtual biological system. This process works on the basis of specific algorithm and involves scoring function to rank the molecules that fit with the target. This study has been designed to investigate the potentiality of four phytochemicals from Clitoria ternatea—Kaempferol, Myricetin, P-Hydroxycinnamic acid and Quercetin as inhibitors of two cell cycle checkpoint proteins—Cyclin Dependent Kinase-2 (CDK-2) and Cyclin Dependent Kinase-6 (CDK-6) in Cyclin/CDK pathway. Quercetin and Myricetin docked with higher affinity with CDK-2 and CDK-6 respectively. Drug likeness property analysis and ADME/T test impose computational approach to investigate physicochemical and pharmacological properties of candidate drug molecules. P-Hydroxycinnamic acid performed well in both drug likeness property analysis and ADME/T than Quercetin and Myricetin. So, P-Hydroxycinnamic acid is the best finding of this experiment.
文摘This experiment has been carried out to observe the potential thrombolytic activity of naturally occuring phytochemicals in Ginger (Zingiber officinale) and to analyze their drug likeness property and ADME/T profile. Thrombolytic activity of Ginger has already been confirmed in laboratory experiment and this study focuses on the molecular interactions among four phytocompounds (Isovanillin, Gingerol, Beta-sitosterol and 2,6-Dimethyl-2-octene-1,8-diol) found in Ginger and Tissue Plasminogen Activator (tPA). Present experiment is largely based on computer-aided drug design protocol where the strength of interaction is described as binding energy function. Isovanillin exhibited better docking score, and so this compound might have greater thrombolytic activity than others. Moreover, Isovanillin also suggested sound drug likeness property and ADME/T profile which predicts its safeness for consumption in human body. But Beta-sitosterol violated Lipinski’s rule of five and 2, 6-Dimethyl-2-octene-1,8-diol showed the lowest affinity of binding with tPA. However, further in vivo or in vitro study may be required to confirm the thrombolytic activity of Isovanillin.
文摘Alzheimer’s Disease (AD) is the most prevalent age-related dementia. AD can be caused by abnormal processing of amyloid precursor protein (APP) or by oxidative stress or may be due to the actions of kinases or the degeneration and loss of functions of neurons in the brain. Although various treatments have already gained success in the in vitro studies, however, till now not a single satisfactory drug has been proven that can cure this disease permanently till now. In this study, the best possible drug has been determined from a group of drug molecules using methods of molecular docking. Molecular docking is a computational approach which helps to determine the best molecule from a group of molecules which may bind with the highest affinity with the intended target by mimicking the original biological environment in a computer. The tested drug molecules in this experiment are the disease modifying agents, capable of inhibiting a particular protein involving in the AD pathway. Eight drug molecules (ligands)-memantine (-4.075 Kcal/mol), hymenialdisine (-8.079 Kcal/mol), tideglusib (-6.445 Kcal/mol), kenpaullone (-7.545 Kcal/mol), dihydrospiro[dibenzo[a,d][7]annulene-5,4’-imidazol] (-4.742 Kcal/mol), harmine (-7.57 Kcal/mol), harmol (-6.583 Kcal/mol) and 1-Methyl-4-Phenylpyridinium (-5.214 Kcal/mol), have been docked successfully against four targets (proteins)-N-Methyl-D-Aspartate Receptor (NMDAR), glycogen synthase kinase-3β (GSK-3β), beta-secretase (β-secretase) and dual specificity tyrosine (Y)-phosphorylation-regulated kinase 1A (DYR-K1A) in this experiment which are intended targets in current AD treatment approaches. Investigation of docking results, druglikeness properties and ADME/T testing results suggest that the best findings of this experiment are memantine, hymenialdisine, dihydrospiro[dibenzo[a,d][7]annulene-5,4’-imi- dazol] and harmol, that could be the best possible drugs for the treatment of AD.
