Proteintyrosine phosphatase 1B(PTP1B)inhibitionis consideredas a potentialtherapeuticfor the treatmentof cancer,type2 diabetes,andobesity.Inour presentwork,weinvestigatedtheanti-diabeticpotentialof8-hydroxydiospyrin(8...Proteintyrosine phosphatase 1B(PTP1B)inhibitionis consideredas a potentialtherapeuticfor the treatmentof cancer,type2 diabetes,andobesity.Inour presentwork,weinvestigatedtheanti-diabeticpotentialof8-hydroxydiospyrin(8-HDN)from D.lotus against the PTP1B enzyme.It showed significant inhibitory activity of PTP1B with an IC 50 value of 18.37±0.02μM.A detailed molecular docking study was carried out to analyze the binding orientation,binding energy,and mechanism of inhibition.A comparative investigation of 8-HDN in the catalytic,as well as the allosteric site of PTP1B,was performed.Binding energy data showed that compound 8-HDN is more selective for the allosteric site and hence avoids the problems associated with catalytic site inhibition.The inhibition mechanism of 8-HDN can be further investigated as an active lead compound against PTP1B by using in vitro and in vivo models.展开更多
The bioactive triterpenoid 3-oxo-6-β-hydroxy-β-amyrin(1)has been isolated from multiple plant sources.In this study,chloroform fraction of Pistacia integerrima extract was processed for the isolation of the compound...The bioactive triterpenoid 3-oxo-6-β-hydroxy-β-amyrin(1)has been isolated from multiple plant sources.In this study,chloroform fraction of Pistacia integerrima extract was processed for the isolation of the compound.The compound identity was confirmed by advanced spectroscopy technique.X-ray crystallography was applied for molecular structure confirmation.In addition,compound 1 was screen for its activity on reversal of MDR(multidrug resistance)mediated by P-gp(P-glycoprotein).This was accomplished by using rhodamine123 exclusion on multidrug-resistant human ABCB1 gene transfected mouse T-lymphoma cell line.Outcomes revealed that MDR reversing effect was comparable to verapamil as positive control in vitro.Treatment of TPA-induced tumor promotion with 3-oxo-6β-hydroxy-β-amyrin led to reduction in the applied anti-tumor promotion experiment.The chemo-preventive effect of 3-oxo-6β-hydroxy-β-amyrin was comparable to curcumin as positive control based on the reduction of immediate early tumor antigen expression.Molecular docking by applying Autodock Vina 1 and i-GEMDOCK v 2.1 tools indicated that compound 1 gives good docking results,as determined by their fitness score and specificity.Moreover,results showed that compound 1 isolated from Pistacia integerrima precisely attached to a region where co-crystallized ligand for receptor previously existed.Our findings may explain the use of Pistacia integerrima plant extracts as an anticancer agent in folk medicine.展开更多
基金funded by Higher Education commission,Pakistan(HEC),Grant No.NRPU649.
文摘Proteintyrosine phosphatase 1B(PTP1B)inhibitionis consideredas a potentialtherapeuticfor the treatmentof cancer,type2 diabetes,andobesity.Inour presentwork,weinvestigatedtheanti-diabeticpotentialof8-hydroxydiospyrin(8-HDN)from D.lotus against the PTP1B enzyme.It showed significant inhibitory activity of PTP1B with an IC 50 value of 18.37±0.02μM.A detailed molecular docking study was carried out to analyze the binding orientation,binding energy,and mechanism of inhibition.A comparative investigation of 8-HDN in the catalytic,as well as the allosteric site of PTP1B,was performed.Binding energy data showed that compound 8-HDN is more selective for the allosteric site and hence avoids the problems associated with catalytic site inhibition.The inhibition mechanism of 8-HDN can be further investigated as an active lead compound against PTP1B by using in vitro and in vivo models.
基金funded by Higher Education commission,Pakistan(HEC)(Grant No.NRPU649).
文摘The bioactive triterpenoid 3-oxo-6-β-hydroxy-β-amyrin(1)has been isolated from multiple plant sources.In this study,chloroform fraction of Pistacia integerrima extract was processed for the isolation of the compound.The compound identity was confirmed by advanced spectroscopy technique.X-ray crystallography was applied for molecular structure confirmation.In addition,compound 1 was screen for its activity on reversal of MDR(multidrug resistance)mediated by P-gp(P-glycoprotein).This was accomplished by using rhodamine123 exclusion on multidrug-resistant human ABCB1 gene transfected mouse T-lymphoma cell line.Outcomes revealed that MDR reversing effect was comparable to verapamil as positive control in vitro.Treatment of TPA-induced tumor promotion with 3-oxo-6β-hydroxy-β-amyrin led to reduction in the applied anti-tumor promotion experiment.The chemo-preventive effect of 3-oxo-6β-hydroxy-β-amyrin was comparable to curcumin as positive control based on the reduction of immediate early tumor antigen expression.Molecular docking by applying Autodock Vina 1 and i-GEMDOCK v 2.1 tools indicated that compound 1 gives good docking results,as determined by their fitness score and specificity.Moreover,results showed that compound 1 isolated from Pistacia integerrima precisely attached to a region where co-crystallized ligand for receptor previously existed.Our findings may explain the use of Pistacia integerrima plant extracts as an anticancer agent in folk medicine.