Synthesis, spectroscopic characterization, stability assessment and DNA-binding of new 2,6-piperidinedione derivatives.

This work reports on structural characterization of new antineoplaston (ANP) representatives, namely 3-(benzoylamino)-2,6-piperidinedione (BPD), 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) and 3-(p-nitrobenzoylamino)-2,6-piperidinedione (NPD). These compounds were prepared by reacting N-(4-substituted benzoyl)-glutamines with N-hydroxysuccinimide to afford the corresponding esters, which were heated to produce the corresponding 2,6-piperidinedione (PD) compounds. Non-destructive analytical procedures such as 1H NMR and NIR analyses confirmed the postulated chemical structures of these PD compounds. HPLC chromatograms at an ambient temperature or from solutions preheated at 30, 40 or 60 degrees C displayed only a single peak for each compound. Combination of heat with pH modification had virtually no effect on the obtained peaks, thus attesting to the stability and purity of these compounds. MS analysis displayed molecular mass ions indicative of BPD, MPD and NPD at m/z 233.4, 263.2 and 278.3, respectively. The fragmentation patterns using MS/MS analyses conformed to the structural and molecular formulae of the prepared compounds. Furthermore, preliminary biological assessments showed the capacity of these compounds to bind to the DNA. NPD, but not BMP or MPD, had a superior affinity to the DNA than the prototype ANP-A10.

Voltametric determination of vancomycin in dosage forms through treatment with nitrous acid.

Two methods are described for the determination of vancomycin (vancomycin hydrochloride, CAS 1404-93-9) in its dosage forms. The two methods involve a prior treatment with nitrous acid then measuring the formed nitroso derivative, either spectrophotometrically or polarographically. In the spectrophotometric method, the absorbance-concentration plot is rectilinear over the range of 4-32 micrograms/ml with minimum detectability of 2.7 micrograms/ml (1.8 x 10(-6) mol/l). The apparent molar absorptivity is 4.084 x 10(-4)l.mol-1.cm-1 and A (1%, 1 cm) is 275. The reaction product was also found to be polarographically reducible at the Dropping Mercury Electrode (DME) with E1/2 of-0.9 V vs. Ag/AgCl electrode and a diffusion current constant (Id) of 0.85 +/- 0.02. The cathodic current produced was found to be diffusion controlled with some adsorption contribution. The calibration plot was linear over the range of 0.015-0.06 mmol l-1 for direct current (DCt) mode and from 0.005-0.05 mmol l-1 for differential pulse polarography (DPP) mode with minimum detectability of 2.4 x 10(-7) mol l-1 using the latter technique. The results obtained were statistically compared with those given with the official B.P. method and were in good agreement.

Spectrofluorimetric determination of streptomycin in dosage forms and in spiked plasma using 9,10-phenanthraquinone.

A simple and highly sensitive method is proposed for the fluorimetric determination of streptomycin in dosage forms and in biological fluids. The method involves the reaction of streptomycin with 9,10-phenanthraquinone in alkaline medium to give a highly fluorescent derivative. The experimental parameters were carefully studied and incorporated into the procedures. The results obtained compared favourably with those obtained by the official methods. The concentration-fluorescence plots were rectilinear over the range 0.025-0.4 microg/ml, with minimum detectability (S/N=2) 0.006 microg/ml (4.19x10(-9) M). The proposed method was applied for the determination of streptomycin in dosage forms. The results obtained were in good agreement with those obtained by the official method. The proposed method was further applied to the determination of streptomycin in human plasma. The percentage recovery was 101.82. A proposal of the reaction pathway was presented.

Kinetic spectrophotometric determination of ampicillin and amoxicillin in dosage forms.

A kinetic spectrophotometric method has been developed for the determination of ampicillin (I) and amoxicillin (II). The method involves hydrolysis of the antibiotics with 1.0 M HCl, neutralization with 1.0 M NaOH followed by addition of palladium(II) chloride in the presence of 2 M KCl. The produced yellow colour is measured at 335 nm. The proposed method is valid over the concentration range 8-40 microg/ml and 10-40 microg/ml for I and II respectively with minimum detectability of 0.73 microg/ml and 0.76 microg/ml for I and II respectively. The determination of the studied compounds adopting the fixed concentration method is feasible with the calibration equations obtained, but the fixed time method has been found to be more applicable. The proposed method was applied to commercial dosage forms and the results obtained were in good agreement with those given by USP method.

Synthesis of some new quinazolines and quinoxalines of potential antiinflammatory activity.

A number of quinazoline derivatives containing basic amine substituents at position 4, as well as new derivatives of triazolo[4,3-alpha]quinoxalines carrying basic amine or carboxylic acid moieties have been synthesized. A tetracyclic imidazotriazoloquinoxaline compound is also reported. Two of the new products (2b and 7b) exhibited good antiinflammatory activity in rats, although inferior to that of indomethacin.

Synthesis and antiinflammatory activity of certain thienopyrimidine derivatives.

Interaction of ethyl 2-amino-4,5,6, 7-tetrahydrobenzo[b]thiophene-3-carboxylate 1 with 2-thiophene carbonyl chloride 2 afforded ethyl 2-(2-thenoylamino)-4, 5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 3 which upon cyclization yielded 2-(2-thienyl)-5,6,7, 8-tetrahydrobenzo[b]-thieno[2,3-d]-4H-3, 1-oxazin-4-one 4 and 2(2-thienyl)-3-amino-5, 6,7,8-tetrahydrobenzo-[b]thieno[2,3-d]-3,4-dihydropyrimidin-4-one 6. Some of the prepared compounds were screened for their antiinflammatory activity, compound 7c and 9b showed significant activity.

Synthesis of certain 2-aminoadamantane derivatives as potential antimicrobial agents.

1-(2-Adamantyl-3-(5-arylhydrazono-6-methyl-4-oxopyrimidin -2-yl)guanidines, 2-(2-adamantylamino)-4-amino-s-triazine and its 6-chloromethyl derivative were prepared by cyclization of 1-(2-adamantyl)biguanide.HCl with ethyl 2-arylhydrazono-3-oxobutyrates, ethyl formate and ethyl chloroacetate, respectively. 1-(2-damantyl)-3-(4,5-dioxo-2-imidazolidinylidene)guanidine was used as intermediate for the synthesis of amides, hydrazide and azomethine derivatives of alkyl 2-(2-adamantylamino)-4-amino-s-triazine-6-carboxylates. The antimicrobial testing of the prepared compounds proved that an azomethine derivative was the most active. It showed a marked bacteriostatic effect against Staphylococcus aureus and Bacillus subtilis.

Preparation of alkoxyquinoline derivatives and their evaluation as potential central nervous system stimulants.

A variety of substituted amides of 6,7-dimethoxy-2-hydroxyquinoline-3-carboxylic acid were synthesized. Three of these compounds, tested as potential central nervous system stimulants, showed no marked biological activity.

Synthesis and antimicrobial testing of 2-substituted styryl-6-nitro-4-quinazolones.

Condensation of 2-methyl-6-nitro-4-quinazolone with different aldehydes was achieved by fusing the reactants in the presence of zinc chloride, affording 2-substituted styryl-6-nitro-4-quinazolones. 2-(3-substituted aminomethyl)-4-hydroxystyryl-6-nitro-4-quinazolones were also prepared through the Mannich reaction. The antimicrobial testing of five of the compounds prepared showed that some of them produce promising effects.

[Thienyl acrylamides and thienyl pyrazolines as potential schistosomicidal agents].

Alpha-Thienyl-N-substituted acrylamides that possess analogous structures to known schistosomicidal agents were synthesized. Two chalcones were prepared by condensing alpha-thiophenealdehyde and acetophenone or its o-hydroxy derivative. Cyclization of the chalcones with hydrazine hydrate or monosubstituted hydrazines afforded 1.3.5 trisubstituted 2-pyrazoline

Synthesis of morpholinobiguanide derivatives.

Several new morpholinobiguanide derivatives were synthesized to be tested as hypoglycemic agents, by condensing morpholinobiguanide with alkyl or aryl isocyanate and isothiocyanate, and with dialkylaminoalkyl chloride. The carbamate, prepared from morpholinobiguanide and ethyl chloroformate, was condensed with different aryl amines and certain sulpha drugs. Most of the prepared compounds are easily soluble in water and preliminary examinations as hypoglycemics show promising results.