Synthesis and antimicrobial activity of γ-bromopropargyl esters of carbamic acids

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 25, No. 6, pp. 47–48, June, 1991.     

Synthesis and antimicrobial activity of monoalkylcarbamic and thiocarbamic esters of 3-mercapto-1,2,4-benzothiadiazine-1,1-dioxide and of its Bz-derivatives

A new series of monoalkylcarbamic esters of 3-mercapto-1,2,4-benzothiadiazine-1,1-dioxide (I) and of its 6-chloro- and 5,7-dichloroderivatives [compounds (II leads to XVI)] and a series of monoalkylthiocarbamic esters of (I) [compounds (XVII leads to XIX)] were synthesized and evaluated in vitro for antimicrobial activity. All the substances studied have been found to possess an inhibiting action on one or more strains of mycetes of the genus Candida and on some strains of Gram-positive bacteria belonging to the genus Staphylococcus. Moreover, some compounds have shown a bacteriostatic effect on a strain belonging to the genus Streptococcus. None of the substances tested was active on Gram-negative schizomycetes.     

Synthesis, pharmacologic and toxicologic study of carbonic and carbamic acid esters

The results of the pharmacologic study of some synthesized derivatives of carbamic and carbonic acids show that the compounds are biologically active. They are less toxic than imipramine, and exert a marked excitation effect on the central nervous system. Some of the compounds (including PS-1, P-8-Y and PS-4) possess greater antidepressive action than imipramine.     

Preparation and antifungal activity of spray-dried amphotericin B-loaded nanospheres

Background and the purpose of the study

Amphotericin B (AmB) which is an appropriate antibiotic for the treatment of mycosis has many toxic effects including nephrotoxicity. Recently preparation of a new drug loaded nanoparticles for the reduction of toxicity and increase in the effectiveness of AmB has been reported. The objective of this study was to prepare and evaluate in vitro and in vivo efficacy of the spray-dried AmB-loaded nanospheres.

Methods

AmB-loaded nanospheres was prepared by means of nanoprecipitation method. The spray-dried nanospheres was prepared by using aerosil and AmB entrapment efficacy was measured by HPLC method. Minimum inhibitory concentration (MIC) of AmB-loaded nanospheres against Candida albicans (ATCC 90028) was determined by using microdilution method and its in vitro haemolytic effect and antifungal efficacy on infected rabbits was also analyzed.

Results

The entrapment efficacy for AmB loaded nanospheres was 65.2%±3. The MIC of AmB-loaded nanospheres against C. albicans compared to the free antibiotic was lower significantly. Also, the AmB-loaded nanospheres found to be 9.5 times less toxic than free AmB on human red blood cells. In vivo testing indicated that AmB-loaded nanospheres have a stronger protective effect against candidiasis compared to the free AmB.

Conclusion

Results of this study suggest that prepared spray-dried AmB-loaded nanospheres would be a good choice for the treatment of mycosis because of low toxicity and high stability and effectiveness.     

Physicochemical properties and antifungal activity of amphotericin B incorporated in cholesteryl carbonate esters

The antifungal activity of amphotericin B (AmB) incorporated in three cholesteryl carbonate esters (CCEs), sodium cholesteryl carbonate, cholesteryl palmityl carbonate, and dicholesteryl carbonate, was examined to assess their potential for use in a dry powder aerosol. Formulations containing dissolved AmB were stable for 6 months. The particle size varied inversely with liquid crystalline content with observed mass median aerodynamic diameters ranging from 4 to 8 μ m. This was consistent with the visual appearance of the liquid crystals as being low density and free flowing at room temperature. When dispersed in water, the presence of the CCE reduced the rate and extent of AmB release, consistent with the estimated liquid crystal/water partition coefficient. Nevertheless, the rate of AmB release was always sufficient to kill the fungus as established with bioactivity studies. AmB formulated with CCE as a dry powder appears to be promising for use in treating lung fungal infections.     

Aminopyridine carbamic acid esters: synthesis and potential as acetylcholinesterase inhibitors and acetylcholine releasers.

4-Amino-3-pyridyl carbamates (2a-c) were synthesized as potential acetylcholinesterase inhibitors and acetylcholine releasers on the basis of the reported activity of the analogous N-(4-amino-3-pyridyl)-N',N'-dimethylurea (1). Although 4-amino-3-pyridyl N,N-dimethylcarbamate (2b) showed good cholinesterase inhibition [concentration that elicited a 50% reduction in the maximal enzyme response (IC50) was 13.4 microM], it had no effect on the stimulated release of [3H]acetylcholine from rat striatal slices. 4-[[(Dimethylamino)methylene]amino]-3-pyridyl N,N-dimethylcarbamate (7a), an intermediate in the synthesis of 2b, demonstrated surprisingly good cholinesterase inhibition (IC50 was 9.4 microM) but showed no activity as a release. A precursor to 7a, N-(3-hydroxy-4-pyridyl)-N',N'-dimethylformamidine (6a), showed some activity in release but was not an esterase inhibitor, whereas the precursor to 6a, 4-amino-3-pyridinol (5a), was a potent releaser. A new synthesis of 5a, based on an ortho-directed lithiation strategy, is also reported.     

Synthesis and antibacterial and antifungal activity of 2-thiocyanato-2-methyl-3-arylpropionic acid allyl esters

Allyl esters of 2-thiocyanato-2-methyl-3-arylpropionic acids exhibit pronounced antibacterial activity with respect to various test strains of staphylococci, colon bacilli, aerobic bacilli, and yeast fungi. The maximum activity is observed for compounds containing chlorine or bromine atoms at the aromatic nucleus. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 11, pp. 27–28, November, 2007.     

Selenium heterocycles XVIII: Synthesis and antibacterial activity of 4-substituted (1,2,3-selenadiazol-5-yl) carbamic acid esters and their sulfur analogs.

4-Substituted (1,2,3-selenadiazol-5-yl)carbamic acid esters and their sulfur analogs were prepared from the Curtius rearrangement of the corresponding carboxazides. None of the compounds showed significant antibacterial activity.