ABSTRACT
A sample of 0.104 M nicardipine in methanol was photoirradiated with a Philips 400 W UV lamp for 3 h in a photochemical chamber. A total of four major photoproducts were found from the HPLC chromatogram. The same sample was used for taking LC-MS, while eight major photoproducts were observed and the structures elucidated by analyzing the CID patterns of their respective mass spectra. A reaction scheme of nicardipine is proposed that the photochemical reactions occur mainly via oxidation of 1,4-dihydropyridine moiety, following the stepwise photo-reduction of the m-nitro group and demethylation of the ester group at 5-position of the pyridine ring.
Subject(s)
Calcium Channel Blockers/chemistry , Calcium Channel Blockers/isolation & purification , Chromatography, High Pressure Liquid/methods , Nicardipine/chemistry , Nicardipine/isolation & purification , Spectrometry, Mass, Electrospray Ionization/methods , Nicardipine/analogs & derivatives , PhotochemistryABSTRACT
A sample of 10 mM flurbiprofen in methanol (or ethanol) was photoirradiated with sixteen 8 W low-pressure quartz mercury lamps irradiated at 306 nm in a Panchum PR-2000 photochemical reactor. In total, four major photoproducts derived from each sample were observed from the HPLC chromatogram. The photoproducts were separated and their structures elucidated by various spectroscopic methods. Alternatively, using GC-MS, 11 major photoproducts were observed. A reaction scheme of flurbiprofen in methanol is proposed: the photochemical reaction routes occur mainly via esterification and decarboxylation, followed by oxidation with singlet oxygen to produce a ketone, alcohols and other derivatives.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/analysis , Flurbiprofen/analysis , Gas Chromatography-Mass Spectrometry/methods , Methanol/chemistry , Chromatography, High Pressure Liquid/methods , Photochemistry , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
Indomethacin is used as an anti-inflammatory drug and a nonselective cyclooxygenase inhibitor. When indomethacin in methanol was photo-irradiated with an Hg lamp, methyl ester, ethyl ester, and gamma-lactone derivatives of indomethacin were produced. In the present study, we found that the methyl ester derivative of indomethacin (M-IN) could more potently inhibit prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX 2) protein expression from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than indomethacin, similar to the effect of a non-steroidal anti-inflammatory drugs (NSAID). On the other hand, the results showed that M-IN with an IC(50) value maintained at 36.9 microg/ml for 12 h exhibited stronger cytotoxicity than ethyl ester, gamma-lactone derivatives of indomethacin, and indomethacin in promyelocytic leukemia HL-60 cells. Moreover, a series of biochemical analyses determined that M-IN caused apoptotic bodies, DNA fragmentation, and enhanced PARP and pro-caspase 3 degradation in HL-60 cells. These above results indicate that the photosynthesized product, M-IN, had stronger anti-inflammatory effects in LPS-stimulated RAW 264.7 cells and cytotoxicity effects in HL-60 cells than the parent drug, indomethacin.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Apoptosis/drug effects , Indomethacin/analogs & derivatives , Indomethacin/therapeutic use , Inflammation/prevention & control , Leukemia, Promyelocytic, Acute/pathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/antagonists & inhibitors , Apoptosis/genetics , Caspase 3 , Caspase Inhibitors , Caspases/metabolism , Cell Survival/drug effects , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , DNA Fragmentation/drug effects , DNA Fragmentation/genetics , Dinoprostone/antagonists & inhibitors , Dinoprostone/genetics , Dinoprostone/metabolism , Dose-Response Relationship, Drug , Formazans , G1 Phase/drug effects , Gene Expression/drug effects , Gene Expression/genetics , HL-60 Cells , Humans , Indomethacin/antagonists & inhibitors , Inflammation/drug therapy , Inhibitory Concentration 50 , Lipopolysaccharides/pharmacology , Methods , Mice , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/drug effects , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Tetrazolium SaltsABSTRACT
A sample of 10 mm zomepirac in methanol was photo-irradiated with a Hanovia 200 W high-pressure quartz Hg lamp for 14 days. In total, four photoproducts were observed from the HPLC chromatogram. The preparative HPLC included an YMC-Pack Pro C18 column (250 x 20 mm i.d.), a mobile phase of CH3CN-CH3OH-1%HOAc (10:60:30, v/v/v), and UV detection at 254 nm. The most probable structures of the four photoproducts were determined by LC-MS. Two major photoproducts were separated, and their structures were further confirmed by the spectroscopic methods. A reaction scheme of zomepirac was proposed that the photochemical reaction routes occur mainly via bond fission between carbonyl-pyrrolyl groups (alpha-cleavage of a ketone), and decarboxylation followed by oxidation with singlet oxygen to produce an aldehyde.
