Raafat Soliman

A sensitive colorimetric method for estimation of ascorbic acid

The reaction of ascorbic acid with ammonium molybdate to give molybdenum blue was investigated and used for microestimation of the vitamin in the pure state, dosage forms and plasma. The proposed method couples sensitivity (as little as 2 microg/ml can be determined) and specificity since no interference was found in the presence of common reducing sugars, antioxidants and degradation products of the vitamin. Recovery varied from 98.9 to 102.3% +/- 0.2-0.5%.

Synthesis of new series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones for their bacterial and cyclin-dependent kinases (CDKs) inhibitory activities

Two series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones were designed, synthesised, and evaluated for their antibacterial activities and CDKs inhibitory activities. The pyridazine derivative: 6-phenyl-5-phenylhydrazono-2,3,4,5-tetrahydropyridazine-3,4-dione (3a) revealed activity against Staphylococcus aureus as Gram-positive bacteria while compound 2-(2-Ethoxyphenyl-5-Phenylpiperazinosulfonamido)-3H-pyrido[2,3-d]pyrimidin-4-one (13c) was showing moderate antifungal activity against Candida albicans.

Synthesis of thiazolo[4,5-d]pyrimidine derivatives as potential antimicrobial agents.

In this study, we report the synthesis and antimicrobial evaluation of several new thiazolo[4,5-d] pyrimidine derivatives, namely 7-substituted amino-5-methyl-3-phenylthiazolo[4,5-d]pyrimi-dine-2 (3H)-thiones4a- e,8,13,15, ethyl 2-cyano-2-(7-substituted-5-methyl-3-phenylthiazolo [4,5-d]-pyrimidin-2(3H)-ylidene)acetates5a- b, 2-(7-substituted-5-methyl-3-phenylthiazolo[4,5-d] pyrimidin-2(3H)-ylidene)malononitriles6a- b, 5-methyl-7-morpholino-3-phenylthiazolo[4,5-d] pyrimidine-2(3H)-one 7, and 7-[4-(1-substituted-5-phenyl-4,5-dihydro-1H-pyrazolin-3-yl)anilino]-5-methyl-3-phenylthiazolo[4,5-d]pyrimidine-2(3H)-thiones10- 12. Some of the tested compounds were more active againstC. albicans thanE. coli andP. aeruginosa, and all were inactive against S.aureus.

Reactions of l-ascorbic and isoascorbic acids with hydrazines related to sulfanilamide drugs

Abstract Various compounds related to the antibacterial, sulfanilamide drugs have been prepared from dehydro- l -ascorbic acid or its d -erythro analog by reaction with hydrazines related to sulfanilamide, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxydiazine, whereby the 2-mono- and 2,3-bis-(hydrazone) were isolated. After opening of the lactone ring in the bis(hydrazones) with alkali, nucleophilic attack, on the carbonyl group, of the imino nitrogen atom of the 3-hydrazone residue afforded 3-( l -threo-glycerol-1-yl)-1-phenyl- and -1-(p-sulfamylphenyl)-4,5-pyrazole-dione 4-(p-sulfamylphenlhydrazone) and the related 3-( d -erythro-glycerol-1-yl)compounds. Whereas acetylation of l -threo-2,3-hexodiulosono-1,4-lactone 2,3-bis(p-sulfamylphenylhydrazone) (9) and 3-( l -threo-glycerol-1-yl)-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone) (15) gave the O-acetyl derivatives, benzoylation of 15 gave the di-N-benzoy ltri-O-benzoyl compound. Reaction of 9 with cupric chloride gave 3,6-anhydro-3-(p-suIfamylphenylazo) - l -xylo-2-hexulosono-1,4-lactone 2-(p-sulfamylphenylhydrazone). The 3-( l -threo-glycerol-1-yl)-1-(p-sulfamylphenyl)flavazole (35) was prepared by the rearrangement of 3-[(1-p-sulfamylphenyl)hydrazono- l -threo-trihydroxybutyl]-2-quinoxalinont (33). Periodate oxidation of 15,33, and 35 gave 3-formyl-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone), 3-1-[(p-sulfamylphenyl)hydrazono]glyoxal-1-yl]-2-quinoxalinone, and 3-formyl-1-(p-sulfamylphenyl)flavazole, respectively. The i.r. and n.m.r. spectral data for some of these derivatives are reported.

Synthesis and biological evaluation of novel series of thieno[2,3-d]pyrimidine derivatives as anticancer and antimicrobial agents

The present study is concerned with the synthesis, anticancer and antimicrobial screening of several new 3-substituted or 2,3-disubstituted-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamide derivatives. Three compounds (4b, 8c, and 11b) were selected by the National Cancer Institute and were first evaluated at a single-dose primary anticancer assay against 60 human cancer cell lines for their in vitro anticancer activity. Compound 8c which passed the criteria for activity in this assay was evaluated against the full panel of 60 human cancer cell lines at five concentrations at tenfold dilutions where it showed non-selective broad-spectrum activity against all cancer cell lines. Furthermore, compounds 4b, 6, 8c, 8d, and 16 showed pronounced antibacterial activities comparable to ampicillin against P. aeruginosa. Therefore, it was concluded that compound 8c may serve as a useful lead compound in search for powerful dual anticancer-antimicrobial agents.

Synthesis and GC-Eims Analyses of Optically Pure 3-Hydroxy-2-Azetidinones Having N-Sulfonamide Drugs Side Chain

Abstract A series of new N-sulfonamides of substituted 3-hydroxy-2-azetidinones were prepared by the [2+2] cycloaddition of aldoximes, formed from the condensation of D-(R)-glyceraldehyde acetonide and the potent p-aminophenyl-N-substituted sulfonamides, with benzyloxyacetyl chloride followed by removal of the protecting groups. Obtaining both diastereoisomeric forms of β-lactams by resorting to kinetic resolution starting from racemic imino analogue is also described. The GC-EIMS, spectroscopic and analytical analyses for some of these derivatives are reported.

Synthesis and Antidiabetic Activity of Some Sulfonylurea Derivatives of 3,4,5-Trisubstituted Pyrazoles

Three series of 3,4,5-trisubstituted pyrazolesulfonylurea derivatives were prepared and evaluated as hypoglycemic agents. Preliminary biological testing revealed that the new compounds possess moderate hypoglycemic activity.

Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents.

A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique. Their antipyretic activity was also evaluated. The results revealed that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic activities. Compounds 5a, 6a and 8a displayed good antipyretic activity. Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition of COX-1. Additionally, the most active compounds were shown to have a large safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a with COX-2 showed good binding profile. Antimicrobial evaluation proved that most of the compounds exhibited distinctive activity against the gram negative bacteria, P. aeruginosa and E coli.

Synthesis and Biological Evaluation of Some Novel Thieno[2,3-d] pyrimidine Derivatives as Potential Anti-inflammatory and Analgesic Agents

A novel series of thienopyrimidine derivatives bearing various substituents or linked to various heterocyclic moieties through atoms spacers were prepared starting from 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6- carboxamide potassium salt 3. Twelve out of the prepared compounds were selected and evaluated for their antiinflammatory activity using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays using diclofenac sodium as a reference standard. The ulcerogenic effects and acute toxicity (ALD50) values of these compounds were also determined. In addition, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. The results revealed that compounds 5a, 13, 14b, 15a, 16a and 16b had high anti-inflammatory effect comparable to diclofenac sodium, whereas compounds 5a, 14a, 15a and 16a revealed pronounced analgesic activity that is equal or higher than that of the reference. All of the tested compounds revealed high GI safety profile and were well tolerated by the experimental animals with high safety margin (ALD50 > 3.0g/Kg).

Synthesis and Antimicrobial Activity of Novel 3-Benzyloxy-4-Substituted-2- Azetidinones: Formation of a Hydrophobic Layer Via a Self-Organization Effect

Abstract We report the synthesis of new persulfide-spacer N-substituted-2-azetidinone-D-glucosamine in an attempt to potentially provide new antibiotics. The Schiff base ligands considered for this study were derived from D-glucosamine and 2-hydroxybenzaldehyde, 4-methoxy-benzaldehyde, cinnamaldehyde, 4-chlorobenzaldehyde, and 4-hydroxy-3-methoxy-benzaldehyde. Staudinger [2+2] cycloaddition of benzyloxyacetyl chloride to the newly reported per-O-allyl-N-substituted benzylidene-2-deoxy-β-D-glucosamine provided the sugar-based monocyclic β-lactams in moderate yields. Radical addition of 2-mercaptoethanol catalyzed by azobisisobutyronitrile to the per-O-allyl-N-substituted-2-azetidinone-D-glucosamine led to the corresponding persulfide-spacers in good yields. All new compounds were characterized by spectroscopic and spectrometric methods. The scanning electron microscopy image of 1,3,4,6-tetra-O-[3-(hydroxythioethyl)-propyl]-2-deoxy-2-N-[(3-benzyloxy-4-(4-chloropenyl)-2-azetidinone]-β-D-glucopyranoside, as a representative example, demonstrated a super hydrophobic layer formed via highly organized thioether spacers on gold as the adsorbate system through the formation of sulfur–gold bonds. The reported glucosides showed a moderate antifungal activity against Candida albicans while being slightly to moderately active against gram-positive and gram-negative bacteria used in this investigation at a concentration of 1 mg/mL dissolved in dimethyl sulfoxide. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT