The enzyme leukotriene A4 (LTA4) plays an important role as precursor of slow reactive substances as LTC4, LTD4, and LTE4. It is an attractive target for molecular modeling and QSAR study. Our effort is mainly focused...The enzyme leukotriene A4 (LTA4) plays an important role as precursor of slow reactive substances as LTC4, LTD4, and LTE4. It is an attractive target for molecular modeling and QSAR study. Our effort is mainly focused on exploring the SAR for inhibitors of the LTA4 hydrolase through docking study, pharmacophore modeling and molecular descriptor study. The binding of these small molecules on LTA4 hydrolase enzyme was described by the models developed on 2D molecular descriptors, with good predictive power (39 compounds, 6 descriptors, r2 0.98, SEE 0.167, F-value 268.53, q2 0.90, r2adj 0.97, P-value < 0.0001, SD of residuals 0.15). Docking studies were employed to presume the probable binding conformation of these analogues and exploring the SAR for the compounds. The novel pharmacophore represents the ligand features that are involved in interactions with the target protein, as well as the space around the ligand occupied by the protein. The efforts are aimed to discover the SAR for the inhibitors of LTA4 hydrolase through techniques of QSAR, docking and pharmacophore.展开更多
Two simple and rapid spectrofluorimetric and spectrophotometric methods were described for the determination of ropinirole hydrochloride content in pharmaceutical dosage forms. Both methods are based on the reaction o...Two simple and rapid spectrofluorimetric and spectrophotometric methods were described for the determination of ropinirole hydrochloride content in pharmaceutical dosage forms. Both methods are based on the reaction of ropinirole hydrochloride and eosin Y in aqueous medium at p H 4.0. Quenching of the fluorescence intensity of eosin Y at 540 nm upon excitation at 350 nm was used for the determination of ropinirole hydrochloride levels after ion-pair complex formation. Also, the absorbance increase of eosin Y at 546 nm after ion-pair complex formation was used for spectrophotometric measurements. Both methods showed linear relationships between the fluorescence quenching or absorbance increase and ropinirole concentration in the range of 6–150 μg/m L and 50–500 μg/m L for spectrofluorimetric and spectrophotometric methods, respectively. As no organic solvents were used in these two methods, they could be categorized as green analytical methods. Both methods were accurate(Error<1.2%) and precise(CV<1.9%), as shown by statistical analysis results. Both methods were used for determination of ropinirole hydrochloride content in pharmaceutical dosage forms without any significant interference from associated impurities.展开更多
Objective: To investigate the antiviral property of a lead ligand, YK51 that was synthesized based on the flavanoid of a natural product toward dengue virus type-2(DENV2)replication.Methods: c RNA was isolated from He...Objective: To investigate the antiviral property of a lead ligand, YK51 that was synthesized based on the flavanoid of a natural product toward dengue virus type-2(DENV2)replication.Methods: c RNA was isolated from HepG2 cells inoculated with 1 000 median tissue culture infective dose of DENV2 and treated with different doses of the ligand followed by RT-PCR to quantify the virus gene copies. Confocal microscopy of actin and tubulin redistribution was also performed.Results: The quantitative RT-PCR result showed reduction of the DENV2 gene copies as the ligand concentration was increased. The confocal microscopy result showed increase in the tubulin intensity(79.6%) of infected BHK21 cells treated with the ligand,compared with the non-treated cells(54.8%). The 1.5-fold increase in the intensity of tubulin suggested that the ligand inhibitory effect stabilized the cellular microtubule structure.Conclusions: The synthesized ligand YK51 reduced DENV2 viral load by inhibiting virus replication thus is highly potential to be developed as antiviral agent.展开更多
A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NM...A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NMR and GC-MS after a semi-preparative HPLC separation. Under optimized conditions, donepezil was derivatized by 9-fluorenylmethyl chloroformate in chloroform and carbonate buffer at pH 9.5 in the presence of NaI after solid-phase extraction from a plasma sample. The reaction product was quantified on a reversed-phase TRACER EXCEL ODS-A, 5 μm column using a mixture of acetonitrile–10 mM acetate buffer(pH 6.0)–THF(60:35:5, v/v/v) as the mobile phase with fluorescence detection at 264 nm(ex) and 313 nm(em). Fluoxetine was used as the internal standard. The total run-time of the analysis was about 10 min, and a clean chromatogram was obtained. The developed method was linear over the range of 1–100 ng/mL in 500 μL of plasma samples(r2>0.998). The intra-day and inter-day precision values were in the range of 2.6%–11.6%. The limit of quantification was 1 ng/mL.展开更多
The use of intramolecular reactions involving palladium/imidazolium salts to synthesize hetero-cyclic compounds is described. Reactivity of phenyl, ethyl and methyl substituents leading to isolation of various isomeri...The use of intramolecular reactions involving palladium/imidazolium salts to synthesize hetero-cyclic compounds is described. Reactivity of phenyl, ethyl and methyl substituents leading to isolation of various isomeric products is also illustrated. Rearrangement of phenyl intermediates to furnish benzoxazoles is also mentioned.展开更多
基金Project supported by Department of Science and Technology,Govt.of India for Awarding Young Scientist Fellowship (SR/FT/LS-161/2008)
文摘The enzyme leukotriene A4 (LTA4) plays an important role as precursor of slow reactive substances as LTC4, LTD4, and LTE4. It is an attractive target for molecular modeling and QSAR study. Our effort is mainly focused on exploring the SAR for inhibitors of the LTA4 hydrolase through docking study, pharmacophore modeling and molecular descriptor study. The binding of these small molecules on LTA4 hydrolase enzyme was described by the models developed on 2D molecular descriptors, with good predictive power (39 compounds, 6 descriptors, r2 0.98, SEE 0.167, F-value 268.53, q2 0.90, r2adj 0.97, P-value < 0.0001, SD of residuals 0.15). Docking studies were employed to presume the probable binding conformation of these analogues and exploring the SAR for the compounds. The novel pharmacophore represents the ligand features that are involved in interactions with the target protein, as well as the space around the ligand occupied by the protein. The efforts are aimed to discover the SAR for the inhibitors of LTA4 hydrolase through techniques of QSAR, docking and pharmacophore.
文摘Two simple and rapid spectrofluorimetric and spectrophotometric methods were described for the determination of ropinirole hydrochloride content in pharmaceutical dosage forms. Both methods are based on the reaction of ropinirole hydrochloride and eosin Y in aqueous medium at p H 4.0. Quenching of the fluorescence intensity of eosin Y at 540 nm upon excitation at 350 nm was used for the determination of ropinirole hydrochloride levels after ion-pair complex formation. Also, the absorbance increase of eosin Y at 546 nm after ion-pair complex formation was used for spectrophotometric measurements. Both methods showed linear relationships between the fluorescence quenching or absorbance increase and ropinirole concentration in the range of 6–150 μg/m L and 50–500 μg/m L for spectrofluorimetric and spectrophotometric methods, respectively. As no organic solvents were used in these two methods, they could be categorized as green analytical methods. Both methods were accurate(Error<1.2%) and precise(CV<1.9%), as shown by statistical analysis results. Both methods were used for determination of ropinirole hydrochloride content in pharmaceutical dosage forms without any significant interference from associated impurities.
基金Supported by Science Fund from the Ministry of Science,Technology and Innovation Malaysia and Research Acculturation Grants of Universiti Teknologi MARA(UiTM)[RAGS/2012/Ui TM/ST04/1],Malaysia
文摘Objective: To investigate the antiviral property of a lead ligand, YK51 that was synthesized based on the flavanoid of a natural product toward dengue virus type-2(DENV2)replication.Methods: c RNA was isolated from HepG2 cells inoculated with 1 000 median tissue culture infective dose of DENV2 and treated with different doses of the ligand followed by RT-PCR to quantify the virus gene copies. Confocal microscopy of actin and tubulin redistribution was also performed.Results: The quantitative RT-PCR result showed reduction of the DENV2 gene copies as the ligand concentration was increased. The confocal microscopy result showed increase in the tubulin intensity(79.6%) of infected BHK21 cells treated with the ligand,compared with the non-treated cells(54.8%). The 1.5-fold increase in the intensity of tubulin suggested that the ligand inhibitory effect stabilized the cellular microtubule structure.Conclusions: The synthesized ligand YK51 reduced DENV2 viral load by inhibiting virus replication thus is highly potential to be developed as antiviral agent.
文摘A new HPLC method has been developed for determining donepezil in human plasma. To find the optimum conditions, a derivatization reaction was performed in different media, and the reaction product was identified by NMR and GC-MS after a semi-preparative HPLC separation. Under optimized conditions, donepezil was derivatized by 9-fluorenylmethyl chloroformate in chloroform and carbonate buffer at pH 9.5 in the presence of NaI after solid-phase extraction from a plasma sample. The reaction product was quantified on a reversed-phase TRACER EXCEL ODS-A, 5 μm column using a mixture of acetonitrile–10 mM acetate buffer(pH 6.0)–THF(60:35:5, v/v/v) as the mobile phase with fluorescence detection at 264 nm(ex) and 313 nm(em). Fluoxetine was used as the internal standard. The total run-time of the analysis was about 10 min, and a clean chromatogram was obtained. The developed method was linear over the range of 1–100 ng/mL in 500 μL of plasma samples(r2>0.998). The intra-day and inter-day precision values were in the range of 2.6%–11.6%. The limit of quantification was 1 ng/mL.
文摘The use of intramolecular reactions involving palladium/imidazolium salts to synthesize hetero-cyclic compounds is described. Reactivity of phenyl, ethyl and methyl substituents leading to isolation of various isomeric products is also illustrated. Rearrangement of phenyl intermediates to furnish benzoxazoles is also mentioned.
