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Biomedical subjects

M A Khalil

Publications and source records attributed to M A Khalil.

At least 19 recordsLinked to original sources
PubMed1998

Non-steroidal anti-inflammatory agents: synthesis of novel benzopyrazolyl, benzoxazolyl and quinazolinyl derivatives of 4(3 H)-quinazolinones.

Four novel series of 4(3 H)-quinazolinone derivatives have been synthesized by cyclization of the intermediate 3-aryl-2-(6-aryl-2-cyclohexen-1-on-5-yl)-4(3 H)-quinazolinones 3a-f with hydrazine, phenylhydrazine, hydroxylamine and thiourea. The products are 3-aryl-2-(6-aryl-3-methyl-1 H-4,5-dihydrobenzo[d]pyrazol-4-yl)-4(3 H)-quinazolinones 4a-f; 3-aryl-2-(6-aryl-3-methyl-1-phenyl-1 H-4,5-dihydrobenzo[d]pyrazol-4-yl)-4(3 H)-quinazolinones 4g-1; 3-aryl-2-(6-aryl-3-methyl-4,5-dihydrobenzo[d]-1,2-oxazol-4-yl)-4(3 H)-quinazolinones 5a-f, and 3-aryl-2-(7-aryl-4-methyl-5,6-dihydro-2(1 H)thioxoquinazolin-5-yl)-4(3 H)-quinazolinones 6a-f. Some of these compounds showed anti-inflammatory activity comparable to or higher than that of the reference compound proquazone.

Animals↗
PubMed1995

Steroidal anti-inflammatory antedrugs: synthesis and pharmacological evaluation of 16 alpha-alkoxycarbonyl-17-deoxyprednisolone derivatives.

In a continuing effort to minimize the systemic adverse effects of potent anti-inflammatory steroids, a series of 16 alpha-alkoxycarbonyl-17-deoxyprednisolone derivatives: methyl (8a), ethyl (8b), isopropyl (8c), and benzyl (8d) 11 beta,21-dihydroxy-3,20-dioxo-1,4-pregnadiene-16 alpha-carboxylate, was synthesized and evaluated for their topical and local anti-inflammatory activities. In the acute croton oil-induced ear edema dose-response bioassay, the topical anti-inflammatory potencies of these esters relative to prednisolone, 1, were: 8a:1.0, 8b:1.3, 8c:4.0, 8a:4.7 and 1:1.0. The putative metabolite, 11 beta,21-dihydroxy-3,20-dioxo-1,4-pregnadiene-16 alpha-carboxylic acid, 7, was inactive in this test. A seven day cotton pellet granuloma bioassay was employed to study the local and systemic anti-inflammatory activities of these steroids. The local anti-inflammatory potencies of these esters relative to prednisolone, 1, were 1.3, 1.5, 2.3, 2.5, and 1.0 for 8a, 8b, 8c, 8d, and 1, respectively. In this semi-chronic study, only prednisolone exhibited significant untoward side effects, such as reduction in thymus weights, normal body weight gain, and normal plasma corticosterone levels. The increase in the topical and local potencies of these steroid esters was consistent with the increase in their 1-octanol/buffer partition coefficient. The ratio of local to systemic anti-inflammatory activity of 8c and 8d was four times that of prednisolone. The effects of increasing the size of the alkoxy group of these new steroids on both topical and local anti-inflammatory activity and their concomitant decrease in untoward systemic effects were unequivocally demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1994

Non-steroidal anti-inflammatory agents: novel pyrazolyl-, 1,2-oxazolyl-, and 1,3-diazinyl derivatives of 4(3H)-quinazolinones.

Four novel series of 4(3H)-quinazolinone derivatives have been prepared by cyclization of the key intermediates 3-aryl-2-(3-aryl-3-oxopropenyl)-4-(3H)-quinazolinones with different reagents: 3-aryl-1-iminocarbamoyl-1H-pyrazol-5-yl)-4(3H)-quinazolines, 3-aryl-2-(3-aryl-1-thiocarbamoyl-1H-pyrazol-5-yl)-4(3H)-quinazolines, 3-aryl-2-(3-aryl-4,5-dihydro-1,2-oxazol-5-yl)-4(3H)-quinazolinones , and 3-aryl-2-(4-aryl-2-thioxo-1,2,5,6-tetrahydro-1,3-diazin-6-yl )-4(3H)- quinazolinones. The antiinflammatory activity of representatives of these compounds is comparable to or higher than that of proquazone.

Animals↗
PubMed1994

Novel fluorinated antiinflammatory steroid with reduced side effects: methyl 9 alpha-fluoroprednisolone-16-carboxylate.

In an effort to test the hypothesis that 9 alpha-fluorination of a steroidal antedrug would enhance receptor binding affinity and local antiinflammatory activity, without concomitantly increasing adverse systemic effects, a fluorinated analog, 10, of methyl 11 beta, 21-dihydroxy- 3,20-dioxo-1,4-pregnadiene-16 alpha-carboxylate (DP16CM, 1) was synthesized and evaluated. In the acute rat croton oil-induced ear edema bioassay, 10 was found to be twice as potent as 1. This increase in topical potency was consistent with enhanced binding affinity of 10, relative to 1. The IC50 values for displacement of [3H]dexamethasone from glucocorticoid receptors of rat hepatoma tissue culture cells were 0.16, 1.2, and 0.03 microM for 10, 1, and prednisolone, respectively. Following multiple topical ID50 applications of predniosolone, 1, and its new fluorinated analog, 10, in the rat subacute croton oil-induced ear edema bioassay, only prednisolone exhibited significant untoward effects, such as reduction in relative thymus and adrenal weights, plasma corticosterone levels, and normal body weight gain. Thus, while fluroination of 1 enhanced its topical potency, there was not a concomitant increase in untoward systemic effects. This lack of adverse systemic effects is ostensibly due to the presence of the metabolically labile 16-carboxylate ester moiety.

Administration, Topical↗
PubMed1994

Percutaneous diskectomy for disk space infections.

To diagnose and treat intervertebral disk space infection, we used percutaneous diskectomy in four patients to harvest a large amount of disk material and to decompress and lavage the infected disk space with a broad spectrum antibiotic solution. This treatment regimen rapidly diminished pain and shortened the acute clinical course of the process. The long-term course in this small number of patients, however, appears not to have been altered.

Acute Disease↗
PubMed1993

Synthesis and antimicrobial evaluation of novel oxa(thia)diazolylquinolines and oxa(thia)diazepino[7,6-b] quinolines.

Three novel series of quinoline derivatives have been prepared by cyclization of the intermediate 3[(substituted)thiocarbamoyl-hydrazonomethyl]-2-chloroquinoline s and 3-aroylhydrazonomethyl-2-chloroquinolines: 3-(3-Acetyl-5-(substituted)-2,3-dihydro-1,3,4-oxa(thia)diazol-2-yl )-2- chloroquinolines (4; 5), 3-(5-(substituted)-1,3,4-oxa(thia)diazol-2-yl)-2-chloroquinolin es (6; 7), and 2-(substituted)-1,3,4-oxa(thia)diazepino[7,6-b]quinolines (8; 9). The antimicrobial activity of these compounds was studied.

4-Quinolones↗
PubMed1992

Repair of symptomatic pseudoarthrosis of anterior cervical fusion. Posterior versus anterior repair.

Thirty-four patients with symptomatic pseudarthrosis of anterior cervical fusion were treated. There were 16 men and 18 women. Eighteen patients had pseudarthrosis at 1 level; 14 at 2 levels; and 2 at 3 levels, with C5-6 and C6-7 levels most commonly involved. Anterior repair of pseudarthrosis was done in 17 patients, which resulted in 76% radiologic fusion. Of 17 patients repaired posteriorly, 94% achieved radiologic fusion. Average follow-up was 60 months, with a minimum of 24 months. "Excellent" or "Good" results were achieved in 59% of anterior repair and 88% of posterior fusion group. This study demonstrates that posterior cervical fusion is the more effective method for repairing symptomatic pseudarthrosis of anterior cervical fusion.

Bone Transplantation↗
PubMed1991

Synthesis of some thiazole-, 1,3,4-thiadiazole-, and 4H-1,2,4-triazole derivatives of pyrazolo[3,4-b]quinoline.

Three novel series of pyrazolo[3,4-b]quinolines were prepared, namely: 1-(3-substituted-4-phenylthiazolin-2-ylidene)hydrazinocarbonylm ethyl-1H-pyrazolo[3,4-b]quinolines 3a-d; 1-(5-substituted amino-1,3,4-thiadiazol-2-yl)methyl-1H-pyrazolo[3,4-b]quinolines 4b-d, and 1-(4-substituted-4H-5- thioxo-1,2,4-triazole-3-yl)methyl-1H-pyrazolo[3,4-b]quinolines 5a-d. These compounds were prepared by cyclization of the new key intermediates 1-(substituted thiocarbamoylhydrazinocarbonyl)methyl-1H- pyrazolo[3,4-b]quinolines 2a-d. The alkylthio, aralkylthio 6a-f as well as the Mannich bases 8a-f derived from compounds 5a-d were also prepared. The structures of the new compounds were elucidated by elemental analyses, IR, 1H-NMR-, and mass spectra. The antimicrobial as well as inotropic and chronotropic activities were studied.

Animals↗
PubMed1991

Correlation of radiologic assessment of lumbar spine fusions with surgical exploration.

Although inspection of posterolateral lumbar fusion is the best method of determining its solidity, routine exploration of the fusion is somewhat impractical because of the morbidity and expense involved. Removal of internal fixation devices or implantable batteries or reoperation for failed back surgery enabled the exploration and assessment of lumbar spine fusions in 214 operations on 175 patients. The preoperative radiologic assessment (plain roentgenographs, polytomography, bending films, and computed tomographic scans) were correlated with surgical findings. This study indicated a significant percentage of inaccuracy of all radiologic modalities used. Noncorrelations were present in 36% of plain roentgenographs, 41% of polytomograms, 38% of bending films, and 43% of computed tomographic scans. Radiologic inaccuracy was manifest on both the positive and negative sides. Computed tomographic scanning presented the lowest percentage of inaccuracy (22%) and bending films the highest percentage (27%). Based on these findings, there exists the need for more accurate noninvasive methods to determine the solidity of spine fusions.

Adult↗
PubMed1990

Synthesis of novel 2-substituted quinoline derivatives: antimicrobial, inotropic, and chronotropic activities.

Three novel series of quinoline derivatives have been prepared by cyclization of the intermediate 3-(1,3-dioxolan-2-yl)-2-substituted thiocarbamoyl-hydrazinoquinolines with different alpha-halocarbonyl compounds. These series are: 3-(1,3-dioxolan-2-yl)-2-(3-substituted-4-phenylthiazolin-2-y lidene) hydrazinoquinolines; 3-(1,3-dioxolan-2-yl)-2-(3-substituted-5-ethoxycarbonyl- 4-methylthiazoline-2-ylidene)hydrazinoquinolines and 3-(1,3-dioxolan-2-yl)-2- (3-substituted-4-thiazolidinon-2-yl)hydrazinoquinolines. The active methylene group of the latter series was used for the preparation of their arylidene derivatives. The antimicrobial as well as inotropic and chronotropic activities of the prepared compounds were studied.

4-Quinolones↗
PubMed1990

Non-steroidal antiinflammatory agents, II: Synthesis of novel pyrazole and pyrazoline derivatives of 4(3H)-quinazolinone.

Antiinflammatory and/or analgesic activities have been ascribed to compounds containing the 4(3H)-quinazolinone or pyrazole moiety. Continuation to the previous work in the field of the synthesis of non-steroidal antiinflammatory 4(3H)-quinazolinones, the present investigation deals with the synthesis of new compounds having the pyrazole or pyrazoline and 4(3H)-quinazolinone moieties in one molecule, hoping that such combination might improve their antiinflammatory activity. alpha,beta-unsaturated ketones when treated with hydrazine hydrate achieve cyclization to the corresponding pyrazoline derivatives, whereas, when arylhydrazines are used, pyrazole derivatives are formed.

Animals↗
PubMed1990

Antilipidemic agents, III: Synthesis of some heterocyclic derivatives of beta-sitosterol.

Four novel series of heterocyclic derivatives of beta-sitosterol were prepared by the reaction of 3-beta-sitosterol hemisuccinate with SOCl2 then with thiols, amines or phenols. These series are: 3 beta-[(3-substituted-4(3H)-quinazolinon-2- yl)thiocarbonylproprionyloxy]stigmast-5-ene; 3 beta- ([4-substituted-5-(4-pyridyl)-4H-1,2,4-triazol-3-yl] thiocarbonylpropionyloxy)stigmast-5-ene; 3 beta- [(5-substituted-1,3,4-thiadiazol-2-yl)carbamoylpropionyloxy] stigmast-5-ene and 3 beta-(substituted carbamoyl or oxycarbonylpropionyloxy)stigmast-5-ene. The antilipidemic activity of representative compounds was studied.

Animals↗
PubMed1990

Synthesis of novel naphtho[2,1-b]-1,4,5-oxa- or thiadiazepines as potential antimicrobial and anticancer agents.

Two novel series of quinone derivatives have been synthesized. Thus, condensation of 2-ethoxycarbonylmethylthio-; 3-ethoxycarbonylmethylthio-2-methyl- and 3-ethoxycarbonylmethoxy-2-methyl derivatives of 1,4-naphthoquinone with substituted phenylhydrazines afforded the corresponding hydrazones, while cyclization of the same quinones with the same substituted hydrazines in glacial acetic acid gave the corresponding naphtho[2,1-b]-1,4,5-oxa- or thiadiazepine derivatives. The antimicrobial and anticancer activities of the synthesized compounds were studied.

Anti-Infective Agents↗
PubMed1990

Non-steroidal antiinflammatory agents. Synthesis of novel 2-pyrazolyl-4(3H)-quinazolinones.

Four novel series of pyrazolyl-4(3H)-quinazolinones have been prepared through the reaction of 3-aryl-2-hydrazino-4(3H)-quinazolinones with antipyrylazo-derivatives of ethyl acetoacetate, acetylacetone or diethyl malonate. These series of compounds are 3-aryl-2-[1-ethoxycarbonyl-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H - pyrazol-4-yl)hydrazono-2-propylidene]hydrazino-4(3H)-quinazo linones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-4(3H)-quinaz olinones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)azo -3,5- dimethyl-1H-pyrazol-1-yl]-4(3H)-quinazolinones and 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3,5-dioxo-pyrazolidin-2-yl]-4(3H)-quinazolinones. The antiinflammatory activity of some representatives of the prepared compounds was studied.

Animals↗
PubMed1990

Synthesis of 3-aryl-2-substituted-4(3H)-quinazolines as potential antimicrobial agents.

Three new series of 4(3H)-quinazolinone derivatives were synthesized, namely: [3-Aryl-4(3H)-quinazolinon-2-yl]-methylenehydrazino-(N- substituted)-thiocarbamides, 3-Aryl-2-(3-substituted-4-phenyl-2,3-dihydrothiazol-2-ylidenehy drazonomethyl)-4 (3H)-quinazolinones and 3-Aryl-2-(3-substituted-4-oxothiazolidin-2-ylidenehydrazonometh yl)-4(3H)-quinazolinones. The antimicrobial activities of the synthesized compounds were also studied.

Anti-Bacterial Agents↗
PubMed1989

Synthesis of some thiazoline and thiazolidinone derivatives of 1,4-benzoquinone as potential antimicrobial agents.

Three novel series of benzoquinone derivatives were synthesized, namely: N-(3-aryl-4-phenylthiazolin-2-ylidene)-N-(1,4-benzoquinone carbonyl) hydrazines; N-(3-aryl-5-carbethoxy-4-methylthiazolin-2-ylidene)-N-(1,4- benzoquinone carbonyl)hydrazine and N-(3-arylthiazolin-4-one-2-ylidene)-N-(1,4- benzoquinone carbonyl) hydrazines. These series were prepared by oxidation of the new hydroquinone precursors. The antimicrobial activity of representative compounds of benzoquinone, as well as of hydroquinone derivatives was studied.

Anti-Bacterial Agents↗