Design, synthesis of 2,3-disubstitued 4(3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents: COX-1/2 inhibitory activities and molecular docking studies.

A new series, 2-substituted mercapto-3-[2-(pyridin-2-yl)ethyl]-4(3H)-quinazolinone 1-21, was synthesized and evaluated for in vivo anti-inflammatory and analgesic activities and in vitro COX-1/COX-2 inhibition. Compounds 1, 4, 5, 6, 8, 10, 13, 14, 15, 16, and 17 exhibited potent anti-inflammatory and analgesic properties, with ED50 values of 50.3-112.

Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibitory activities and molecular docking studies of substituted 2-mercapto-4(3H)-quinazolinones.

A new series of 2-substituted mercapto-4(3H)-quinazolinone 1-26 were synthesized and assessed for in vivo anti-inflammatory and analgesic activities and in vitro inhibition of cyclooxygenase COX-1/COX-2. A new series of 2-substituted mercapto-4(3H)-quinazolinone 1-26 were synthesized and assessed for in vivo anti-inflammatory and analgesic activities. The potent anti-inflammatory compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays.

Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives.

Design, synthesis and pharmacological activities of a group of 1,3,5-trisubstituted pyrazolines were reported. The chemical structures of the synthesized compounds have been assigned on the basis of IR, MS, (1)H NMR, and (13)C NMR spectral analyses. The synthesized 1,3,5-trisubstituted pyrazoline derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay.

Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies.

The design, synthesis and pharmacological activities of a group of 5,5-diphenylimidazolidine-2,4-dione bearing anilide, phenacyl and benzylidene fragments 2-27 were reported. The prepared 5,5-diphenylimidazolidine-2,4-dione derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 5, 9, 10, 13, and 14 showed significant and potent anti-inflammatory and analgesic activities almost equivalent to reference drug celecoxib.

Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: anti-inflammatory and analgesic activities.

A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 = 0.18, 0.

The antidepressant bupropion exerts alleviating properties in an ovariectomized osteoporotic rat model.

Aim: Depression is a risk factor for impaired bone mass and micro-architecture, but several antidepressants were found to increase the incidence of osteoporotic fractures. In the present study we used ovariectomized (OVX) rats as a model of osteoporosis to investigate the effects of the antidepressant bupropion on the femoral bones.

Methods: OVX animals were treated with bupropion (30, 60 mg·kg(-1)·d(-1)) for six weeks.

Synthesis of N-benzenesulfonamide-1H-pyrazoles bearing arylsulfonyl moiety: novel celecoxib analogs as potent anti-inflammatory agents.

The reaction of arylsulfones 11a-d with hydrazonoyl chloride derivative 13 furnished celecoxib analogs 4-(3-acetyl-5-aryl-4-(arylsulfonyl)-1H-pyrazol-1-yl)benzenesulfonamides 15a-d, respectively. Oximes 16a, b and hydrazones 17a, b were prepared by reacting sulfones 11a, b with hydroxyl amine and phenyl hydrazine, respectively. The anti-inflammatory activity of the synthesized compounds showed that, 5-(4-bromophenyl)-4-(phenylsulfonyl)pyrazole 15c and 5-(4-bromophenyl)-4-(4-tolylsulfonyl)pyrazole 15d exhibited excellent anti-inflammatory activity with ED50 = 68 ± 2.

Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of Polygonatum verticillatum.

Background: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.

Methods: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2).

Synthesis and hypoglycemic activity of some new theophylline derivatives.

Thirty-one new theophylline derivatives have been synthesized and evaluated for their hypoglycemic activity. Compounds 24 (56% reduction) and 31 (57% reduction) showed better hypoglycemic activity than the standard drug glibenclamide which showed 52% reduction in serum glucose level. Compound 27 remarkably reduced serum glucose level by 53%.

Molecular design, synthesis and biological evaluation of cyclic imides bearing benzenesulfonamide fragment as potential COX-2 inhibitors. Part 2.

A group of cyclic imides (1-10) was designed for evaluation as a selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activity. Compounds 6a, 6b, 8a, 8b, 9a, 9b, 10a and 10b were proved to be potent COX-2 inhibitors with IC50 range of 0.1-4.

Synthesis and in-silico studies of some diaryltriazole derivatives as potential cyclooxygenase inhibitors.

The synthesis of several 4-phenyl-5-pyridin-4-yl-2,3-dihydro-3H-1,2,4-triazole-3-thiones possessing N-2 Mannich bases or S-alkyl substituents, is reported. Several of them exhibited a low nanomolar COX enzyme inhibition activity. Most of the compounds showed inhibition of edema was similar to that evoked by celocoxib in animal model.

Synthesis, biological evaluation and molecular modeling study of pyrazole and pyrazoline derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Part 2.

New pyrazole and pyrazoline derivatives have been synthesized and their ability to inhibit ovine COX-1/COX-2 isozymes was evaluated using in vitro cyclooxygenase (COX) inhibition assay. Among the tested compounds, N-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene)-3,5-bis(trifluoromethyl)aniline 8d exhibit optimal COX-2 inhibitory potency (IC(50)=0.26 lM) and selectivity (SI)=>192.

Design and synthesis of novel 7-aminoquinazoline derivatives: antitumor and anticonvulsant activities.

A novel series of 7-substituted-4(3H)-quinazolinone were designed, synthesized and evaluated for their antitumor and anticonvulsant activity. Compound 7 revealed broad-spectrum antitumor effectiveness toward numerous cell lines that belong to different tumor subpanels, whereas compounds 9 and 18 possess selective activity toward leukemia cell lines. Additionally, compounds 3, 15, 16, 18, 19 and 20 showed advanced anticonvulsant activity as well as lower neurotoxicity than reference drugs.

Synthesis and anticonvulsant evaluation of some new 2,3,8-trisubstituted-4(3H)-quinazoline derivatives.

A new series of 2,3,8-trisubstituted-4(3H)-quinazoline derivatives were synthesized, evaluated for their anticonvulsant activity against electrically (MES) and chemically (PTZ, picrotoxin and Strychnine) induced seizures and compared with the standard drugs methaqualone and sodium valproate. Compounds 3, 17 and 22 proved to be the most potent compounds of this series with relatively low neurotoxicity and low toxicity in the median lethal dose test as compared with the reference drugs. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs.

Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study.

New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay.

Synthesis, anti-inflammatory activity and COX-1/COX-2 inhibition of novel substituted cyclic imides. Part 1: Molecular docking study.

A group of cyclic imides (1-13) was designed for evaluation as selective COX-2 inhibitors and investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model. Compounds 5b, 6b, 11b, 11c, 12b and 12c were proved to be potent COX-2 inhibitors with IC50 range of 0.1-1.

Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline derivatives.

Two series of some new 2,4,6-trisubstituted-quinazoline derivatives were prepared and screened for their analgesic, anti-inflammatory activity and acute toxicity. Four compounds were more potent analgesic agents than the reference drug Indomethacin and thirteen compounds showed significant anti-inflammatory activity. Seven compounds showed combined ability to inhibit both pain and inflammation.

Influence of cyclodextrin complexation with NSAIDs on NSAID/cold stress-induced gastric ulceration in rats.

The aim of this work was to study the ability of beta-cyclodextrin (beta-CD) or hydroxypropyl beta-cyclodextrin (HP-beta-CD) to ameliorate the induction of gastric ulcers by a nonsteroidal anti-inflammatory drug, indomethacin or piroxicam, in rats exposed to restraint and hypothermic stress at 4 degrees C. Using oral gavage, rats fasted for 72 h were administered the equivalent of a 100 mg/kg dose of the assigned drug, alone or with the designated cyclodextrin (CD). The rats were placed in suitable rodent restrainers and then placed inside a ventilated refrigerator maintained at a temperature of 4 degrees C.