In vitro studies on the transdermal formulation containing pentoxifylline microspheres with poly-L-lactide.

In this study, microspheres of Pentoxifylline (PTX) obtained with poly-L-lactide were investigated for drug-polymer ratios of 1:1, 1:5 and 1:10 and the HPLC results of PTX in the microspheres indicated that 1:5 drug-polymer ratio had the highest loading efficiency. For HPLC analysis acetonitrile-water (40:60) was selected as the mobile phase because it yielded the most favorable k' values. Retention times are 4.51 and 7.88 min. for PTX and internal standard (phanecetin), respectively. Calibration curves were linear (r2 > 0.999) in the range of 0.5-10 mg/ml with no significant difference from the origin. Then, matrix controlled transdermal systems containing plain drug or microspheres of drug were prepared. Carrageenan was chosen as a matrix polymer. In vitro release data of the formulations were evaluated kinetically. The results obtained indicate that PTX containing microspheres can be incorporated in carrageenan matrices to form a transdermal therapeutic system.

Synthesis and preliminary CNS depressant activity evaluation of new 3-[(3-substituted-5-methyl-4-thiazolidinon-2-ylidene)hydrazono]-1H-2- indolinones and 3-[(2-thioxo-3-substituted-4,5-imidazolidinedion-1-yl) imino]-1H-2-indolinones.

A series of (+/-) 3-[(3-substituted-5-methyl-4-thiazolidinon-2- ylidene)hydrazono]-1H-2-indolinones (2a-h) and 3-[(2-thioxo-3-substituted-4,5-imidazolidinedion-1-yl)imino] -1H-2-indolinones (3a-g) were synthesized by the cyclization of 3-(4-substituted-thiosemicarbazono)-1H-2-indolinones (1a-h) with ethyl 2-bromopropionate in anydrous ethanolic medium and oxalyl chloride in anhydrous diethyl ether, respectively. The structures of 2 and 3 were confirmed by analytical and spectral data (IR, 1H NMR, 13C NMR, and EIMS). The configuration of 3 was assigned on the basis of 1H NMR and 13C NMR data. 2c, 2d, 2g, 2h, and 3a-g were evaluated for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazol (ScMet) induced seizures. Among the compounds tested, only 2d exhibited some activity in anticonvulsant identification (Phase I) trials in mice. 2a, 2b, 2d, 2g, 2h, and 3a-g were additionally tested for potentiating effects on pentobarbital induced hypnosis in mice. All of the test compounds increased the sleeping time of pentobarbital significantly (p < 0.05) and the most potent compound was found to be 3a.

Synthesis and structure-activity relationships of 3-hydrazono-1H-2-indolinones with antituberculosis activity.

A series of 3-[S-(4-substituted phenacyl)-4-substituted-isothiosemicarbazono]-1H-2-indolinones+ ++ 2a-h and 3-[(3,4-disubstituted-4-thiazolin-2-ylidene)hydrazono]-1H-2- indolinones 3a-f were synthesized. These new hydrazonoindolinone derivatives and 3-(4-substituted-thiosemicarbazono)-1H/1-acetyl-2-indolinones++ + 1a-g 3-[(2-substituted-4-thiazolidinon-2-ylidene)hydrazono]-1H-2- indolinones 4a-o, 3-[(2-substituted-4-carboxy/carbetoxy-5-methyl-4-thiazolin-2 -ylidene) hydrazono]-1H-2-indolinones 5a-e and 3-substituted-hydrazono-1H-2-indolinones 6a-o which had been previously reported were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv. These compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at 12 micrograms/ml against M. tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. 2a, 2c, 2f-h, 3c and 3f demonstrating activity in the primary screen were re-tested at lower concentrations against M. tuberculosis H37Rv to determine the actual minimum inhibitory concentration (MIC) in CABTEC 460. The structure-activity relationships of the derivatives were investigated.

New 4-thiazoline-2-hydrazono-1H-2-indolinones as possible antimicrobial agents.

In order to test their antimicrobial activity a series of new 3-[(3-substituted-4-methyl-5-carboxy/carbetoxy-4-thiazolin-2 - ylidene)hydrazono]-1H-2-indolinones (3a-i/4) were synthesized from the reaction of 3-(4-substituted-3-thiosemicarbazono-1H-2-indolinones (1a-I) with 2-chloroacetoacetic acid ethyl ester (2). All synthesized compounds were characterized by IR, 1H-NMR, EIMS and elementary analysis.