Crystal engineering concept has been utilized to modify the physico-chemical parameters of a naturally occurring alkaloid, quinine sulphate, by exploring its H-bond interactions to generate different forms. Quinine su...Crystal engineering concept has been utilized to modify the physico-chemical parameters of a naturally occurring alkaloid, quinine sulphate, by exploring its H-bond interactions to generate different forms. Quinine sulphate is found to exist in four different crystal forms. The Forms I and II depict endo/exo events suggesting conversion of metastable low melting forms to higher melting and stable form indicated by sharp melting endotherms. The low melting form IL is found to be monotropically related to high melting Form IH while low melting Form IIL is enantiotropically related to high melting Form IIH. The Form III and IV showed broad endotherms accompanied by mass loss in TGA prior to melting indicating the existence of solvatomorphism. The solvent molecules are tightly bound in the crystal lattice of the drug molecules which is shown by high values of the binding energies of the solvents in these two forms. The enthalpy of solution was found to be endothermic for all the forms which followed the order: Form O > Form II > Form III > Form I > Form IV and is further related to the lattice energy suggesting Form II to be least crystalline. The solubility for Form II was found to be highest with maximum release rate in dissolution studies. The effectiveness of new polymorphic forms was confirmed by performing in vivo antimalarial activity against P. berghei infection. The studies have shown an increase in antimalarial activity of Form IV concluding a successful development of new polymorphic form.展开更多
Cigarette smoking(CS)induced chronic obstructive pulmonary disease(COPD)is third leading cause of global pulmonary health issue.Currently,there is no effective therapeutic strategy to control perpetuating inflammatory...Cigarette smoking(CS)induced chronic obstructive pulmonary disease(COPD)is third leading cause of global pulmonary health issue.Currently,there is no effective therapeutic strategy to control perpetuating inflammatory response in COPD.The aim of current study was to investigate the protective effects of piperine in CS-induced murine model of COPD.Exposure of experimental animals to cigarettes smoke twice daily for 10 weeks resulted in increased production of pro-inflammatory mediators including IL-1β,IL-8,TNF-α,LTB-4 and neutrophil elastase(NE)in bronchoalveolar(BAL)fluid.Oxidative stress biomarkers,malondialdehyde(MDA),myeloperoxidase(MPO),nitric oxide and MMP9 also significantly increased in CS-control mice lungs as compared to normal control group(P<0.001).Moreover,CS also increased recruitment of inflammatory cells,neutrophils and macrophages into BAL fluid and altered breathing rate and tidal volume as compared to normal control mice.However,oral treatment of CS-exposed animals with test drug,piperine(10 mg/kg,b.w.or 20 mg/kg,b.w.)or reference standard methyl prednisolone(3.25 mg/kg,b.w.)for 21 days or 7 days,respectively,significantly(p<0.05,0.01,0.001)improved pulmonary function and reversed CS-induced production of cytokines,oxidative stress biomarkers and other biochemicals as compared to CS-exposed control mice.Further,In silico molecular docking studies exhibited attractive binding affinity of piperine for human neutrophil elastase,MMP-9,MPO and IL-8 receptors.Findings of our study suggest protective effect of piperine in experimental animals by repressing CS-induced infiltration of inflammatory cells and thereby exaggerated production of pro-inflammatory mediators and oxidative stress.展开更多
文摘Crystal engineering concept has been utilized to modify the physico-chemical parameters of a naturally occurring alkaloid, quinine sulphate, by exploring its H-bond interactions to generate different forms. Quinine sulphate is found to exist in four different crystal forms. The Forms I and II depict endo/exo events suggesting conversion of metastable low melting forms to higher melting and stable form indicated by sharp melting endotherms. The low melting form IL is found to be monotropically related to high melting Form IH while low melting Form IIL is enantiotropically related to high melting Form IIH. The Form III and IV showed broad endotherms accompanied by mass loss in TGA prior to melting indicating the existence of solvatomorphism. The solvent molecules are tightly bound in the crystal lattice of the drug molecules which is shown by high values of the binding energies of the solvents in these two forms. The enthalpy of solution was found to be endothermic for all the forms which followed the order: Form O > Form II > Form III > Form I > Form IV and is further related to the lattice energy suggesting Form II to be least crystalline. The solubility for Form II was found to be highest with maximum release rate in dissolution studies. The effectiveness of new polymorphic forms was confirmed by performing in vivo antimalarial activity against P. berghei infection. The studies have shown an increase in antimalarial activity of Form IV concluding a successful development of new polymorphic form.
基金Notice for SRF,45/48/2011/BMS/TRM,dated 28-05-2013.Indian Council of Medical Research(ICMR),India.
文摘Cigarette smoking(CS)induced chronic obstructive pulmonary disease(COPD)is third leading cause of global pulmonary health issue.Currently,there is no effective therapeutic strategy to control perpetuating inflammatory response in COPD.The aim of current study was to investigate the protective effects of piperine in CS-induced murine model of COPD.Exposure of experimental animals to cigarettes smoke twice daily for 10 weeks resulted in increased production of pro-inflammatory mediators including IL-1β,IL-8,TNF-α,LTB-4 and neutrophil elastase(NE)in bronchoalveolar(BAL)fluid.Oxidative stress biomarkers,malondialdehyde(MDA),myeloperoxidase(MPO),nitric oxide and MMP9 also significantly increased in CS-control mice lungs as compared to normal control group(P<0.001).Moreover,CS also increased recruitment of inflammatory cells,neutrophils and macrophages into BAL fluid and altered breathing rate and tidal volume as compared to normal control mice.However,oral treatment of CS-exposed animals with test drug,piperine(10 mg/kg,b.w.or 20 mg/kg,b.w.)or reference standard methyl prednisolone(3.25 mg/kg,b.w.)for 21 days or 7 days,respectively,significantly(p<0.05,0.01,0.001)improved pulmonary function and reversed CS-induced production of cytokines,oxidative stress biomarkers and other biochemicals as compared to CS-exposed control mice.Further,In silico molecular docking studies exhibited attractive binding affinity of piperine for human neutrophil elastase,MMP-9,MPO and IL-8 receptors.Findings of our study suggest protective effect of piperine in experimental animals by repressing CS-induced infiltration of inflammatory cells and thereby exaggerated production of pro-inflammatory mediators and oxidative stress.
