AIMStudies on synthesis and antibacterial activity of new heterocycles.

METHODSThe cyclocondensation of [(3-pyridyl)-1,3,4-oxadiazol-2-yl] thio acetic acid with various aroyl hydrazines in the presence of POCl3 and xylene gave the corresponding titled compounds, and the in vitro antibacterial activity was primarily evaluated by the method of cupplate diffusion solution.

RESULTSSixteen novel titled compounds were synthesized, their structures were confirmed by IR, 1HNMR, MS and elemental analysis. Biological screening results demonstrated that most of the compounds prepared displayed potential antibacterial activity.

CONCLUSIONOxadiazoles incorporting pyridyl oxadiazole ring may be usefully antibacterial candidate drugs.

Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Escherichia coli ; drug effects ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Proteus vulgaris ; drug effects ; Staphylococcus aureus ; drug effects

Hypoxic pulmonary vasoconstriction (HPV), a unique response of pulmonary circulation, is critical to prevent hypoxemia under local hypoventilation. Hypoxic inhibition of K+ channel is known as an important O2-sensing mechanism in HPV. Carbon monoxide (CO) is suggested as a positive regulator of Ca2+-activated K+ channel (BK(Ca)), a stimulator of guanylate cyclase, and an O2-mimetic agent in heme moiety-dependent O2 sensing mechanisms. Here we compared the effects of CO on the HPV (Po2, 3%) in isolated pulmonary artery (HPV(PA)) and in blood-perfused/ventilated lungs (HPV(lung)) of rats. A pretreatment with CO (3%) abolished the HPV(PA) in a reversible manner. The inhibition of HPV(PA) was completely reversed by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. In contrast, the HPV(lung) was only partly decreased by CO. Moreover, the partial inhibition of HPV(lung) by CO was affected neither by the pretreatment with ODQ nor by NO synthase inhibitor (L-NAME). The CO-induced inhibitions of HPV(PA) and HPV(lung) were commonly unaffected by tetraethylammonium (TEA, 2 mM), a blocker of BK(Ca). As a whole, CO inhibits HPV(PA) via activating guanylate cyclase. The inconsistent effects of ODQ on HPV(PA) and HPV(lung) suggest that ODQ may lose its sGC inhibitory action when applied to the blood-containing perfusate.
Animals ; Anoxia/*physiopathology ; Carbon Monoxide/*pharmacology ; Guanylate Cyclase/antagonists & inhibitors/metabolism ; NG-Nitroarginine Methyl Ester/chemistry/pharmacology ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Oxadiazoles/chemistry/pharmacology ; Pulmonary Artery/*physiopathology ; Quinoxalines/chemistry/pharmacology ; Rats ; Tetraethylammonium/chemistry/pharmacology ; Vasoconstriction/*drug effects/physiology

AIMTo synthesize and study the antithrombotic activity of NO-donating aspirin derivatives.

METHODSFuroxans and nitrates were incorporated to aspirin via antioxidant ferulic acid as a linker, and the target compounds were screened for in vitro and in vivo inhibitory activities of platelet aggregation, and for inhibitory effect on A-V hypass thromhosis in rats.

RESULTSFourteen novel compounds I(1-14), were synthesized and their structures were confirmed Iy MS, IR, 1H NMR and elemental analysis. Biological screening results demonstrated that some tested compounds exhibited potential antithrombotic activ it.

CONCLUSIONAcetylsalicyl ferulic acid-coupling furoxans and nitrates might he used as a lead for further study.

Animals ; Aspirin ; chemistry ; Coumaric Acids ; chemistry ; Fibrinolytic Agents ; chemical synthesis ; chemistry ; pharmacology ; Models, Chemical ; Molecular Structure ; Nitrates ; chemistry ; Nitric Oxide Donors ; chemistry ; Oxadiazoles ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Rats

AIMTo study on synthesis and antibacterial activity evaluation of polyheterocycles.

METHODSThe condensation of 4-amino-3-pyridin-3-yl-4H-[1,2,4] triazole-5-thiol with 2-chloromethyl-5-substituted phenyl-[1,3,4] oxadiazoles gave the corresponding title heterocycle amines, and the in vitro antibacterial activity was primarily evaluated by the method of cup-plate diffusion solution.

RESULTSTwelve novel compounds were synthesized, and their structures were confirmed by IR, 1H NMR, MS and element analysis. Biological screening results demonstrated that most of the compounds prepared showed good antibacterial activity.

CONCLUSIONOxadiazoles incorporting pyridyl triazole ring may be a pharmacophor structure in the molecule for developing antibacterial candidate drugs.

Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Escherichia coli ; drug effects ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Proteus vulgaris ; drug effects ; Staphylococcus aureus ; drug effects ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

AIMTo search for novel antiasthmatic agents.

METHODSCoupling seratrodast (SD), an antiasthmatic drug, with several different types of NO donors including oxatriazoles, N-hydroxyguanidines and furoxans; evaluating the antiasthmatic effects of coupled compounds by determining their inhibitory activity of guinea pig asthma induced by acetylcholine and histamine; and assessing NO releasing ability.

RESULTSNine novel target compounds (I1-9) were synthesized, and their structures were established by IR, NMR, MS and elemental analysis. Preliminary pharmacological test showed that most of the compounds showed high antiasthmatic activities (the latent period of induced asthma was prolonged from 10 s (SD) to 26-62 s), among which 3 compounds (I4, I6, I7) were more potent than SD (P < 0.05, P < 0.01) and released more NO than others. The maximum concentrations (Cmax) of NO-release in vitro were 0.1878, 0.1393 and 0.2473 mg x L(-1), respectively.

CONCLUSIONNO donating-SD derivatives are worthy to be futher investigated.

Acetylcholine ; Animals ; Anti-Asthmatic Agents ; chemical synthesis ; pharmacology ; therapeutic use ; Asthma ; chemically induced ; prevention & control ; Benzoquinones ; chemical synthesis ; pharmacology ; therapeutic use ; Guanidines ; chemistry ; pharmacology ; Guinea Pigs ; Heptanoic Acids ; chemical synthesis ; pharmacology ; therapeutic use ; Histamine ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; pharmacology ; Oxadiazoles ; chemistry ; pharmacology ; Structure-Activity Relationship

To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin, a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate, oxadiazole thiol (5), which was further modified to the bis-oxadiazole methylsulfides (7a-7h) and the corresponding dimethylpiperazinium iodides (8a-8h), respectively. Structures were characterized by elemental analysis and spectra data, and their anticancer activities in vitro against CHO, HL60 and L1210 cancer cells were also evaluated by MTT assay. The preliminary results show that piperazinium compounds (8) possess more potent activity than that of corresponding free bases (7).
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Ciprofloxacin ; chemistry ; Cricetinae ; Cricetulus ; Drug Design ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; Molecular Structure ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Piperazines ; chemical synthesis ; chemistry ; pharmacology

To develop a new small molecular probe for discovering an antitumor lead compound from the replacement of carboxylic group of two molecular antibacterial fluoroquinolones with a heterocyclic ring, a series of the C3/C3 bis-fluoroquinolones tethered with an 1, 3, 4-oxadiazole ring were synthesized as their respective HCl salts, and their structures were characterized by elemental analysis and spectral data. The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated via the respective IC50 values by methylthiazole trazolium (MTT) assay.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; drug effects ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Drug Design ; Fluoroquinolones ; chemical synthesis ; chemistry ; pharmacology ; HL-60 Cells ; drug effects ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; pathology ; Molecular Structure ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

AIMTo search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects.

METHODSCoupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo.

RESULTSFifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo.

CONCLUSIONCompound II2 is worthy to be intensively studied.

Analgesics ; chemical synthesis ; pharmacology ; therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; chemical synthesis ; pharmacology ; therapeutic use ; Cyclic N-Oxides ; administration & dosage ; chemistry ; pharmacology ; Diclofenac ; chemical synthesis ; pharmacology ; therapeutic use ; Digestive System ; drug effects ; Edema ; drug therapy ; Gastrointestinal Hemorrhage ; chemically induced ; Mice ; Molecular Structure ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; pharmacology ; Oxadiazoles ; administration & dosage ; chemistry ; pharmacology ; Pain Threshold ; drug effects ; Rats ; Structure-Activity Relationship