Enhanced solubility and antibacterial activity of lipophilic fluoro-substituted N-benzoyl-2-aminobenzothiazoles by complexation with ß-cyclodextrins.

Some lipophilic fluoro-substituted N-benzoyl-2-aminobenzothiazole antibacterial agents have been evaluated for their activity in the presence of cyclodextrins (CDs) containing aqueous solutions where CDs are adopted as solubilizing excipients for improving the poor water solubility of these compounds. For such purpose both the natural ß-CD and one of FDA/EMA approved CDs for parenteral use (i.e. HP-ß-CD) have been employed. The solubility rank order observed was accounted for by thermal analysis (Differential Scanning Calorimetry) and FT-IR spectroscopy. The most promising compound was subjected to further NMR spectroscopic studies and molecular modelling simulations to verify the interactions between the guest molecule and the CD cavity. The assessment of the antibacterial activity of such compounds against selected Gram positive and Gram negative bacterial strains clearly showed that their antimicrobial effectiveness may, quite in all instances, be positively affected by complexation with ß-CD and HP-ß-CD. These results, which are in some ways in contrast with those already reported in the literature, are herein discussed on the basis of plausible mechanisms. Moreover, this investigation also reveals that the described methodology of complexing both lipophilic and hydrophilic antimicrobial agents with CDs may be an useful approach to enhance their effectiveness as well as a promising strategy to overcome even the microbial resistance problem.

Research on potentially bioactive aza and thiaza polycyclic compounds containing a bridgehead nitrogen atom. Synthesis and antimicrobial activity of some pyrrolo[1,2,3-de]-1,4-benzothiazines, Part 2.

Acid catalyzed cyclization reactions of both 3-alkyl- and 3-aryl-substituted N-(2,2-dialkoxyethyl)-3,4-dihydro-2H-1,4-benzothiazines (2) lead to 2,3-dihydro-pyrrolo[1,2,3-de]-1,4-benzothiazines (3). The pyrrolobenzothiazine structure was deduced on the basis of 2D 1H NMR-NOESY experiments and fully determined by X-ray data. Compounds 3a-c showed poor antibacterial activity. However, the 3-phenyl-N-(2,2-dimethoxyethyl)-3,4-dihydro-2H-1,4-benzothiazine (2b') showed antifungal activity against Aspergillus niger 16-fold greater than miconazole.

Synthesis and antimicrobial activity of some N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles.

Several N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles (4) were synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria. Compounds 4 were also tested for antifungal activity against Saccharomyces cerevisiae. The findings clearly showed that all the compounds 4 were devoid of antifungal activity, whereas the compounds 4i-m,o-r were effective against the bacterial strains used. Compounds 4k,m,p,q proved to be the most active antibacterial agents showing in some cases minimum inhibitory concentrations (MIC) lower than chloramphenicol and gentamicin, used as reference compounds. In the case of two representative bacterial strains (Gram-positive and Gram-negative, respectively), a parabolic relationship was found between the antibacterial activity of compounds 4i-m,o-r expressed as log1/MIC and the molecular lipophilicity measured as RM values.

Preparation of potentially bioactive aza and thiaza polycyclic compounds containing a bridgehead nitrogen atom synthesis and antimicrobial activity of some pyrrolo[1,2,3-de]-1,4-benzothiazines.

The synthesis of the 2,3-dihydro-pyrrolo[1,2,3-de]-1,4-benzothiazine 1a and 11b, 12-dihydro-isoquino[1,2-c]-1,4-benzothiazine 8 has been accomplished by using a Bischler type cyclization of the N-(2,2-diethoxyethyl)-3,4-dihydro-2H-1,4-benzothiazines 3a and 3d, respectively. The new compounds 1a and 8 together with the known pyrrolobenzothiazines 1b,c and some their derivatives and intermediates of preparation were tested in vitro for their antimicrobial activity. Compound 1b was the most active against the Gram-positive Bacillus subtilis. Compound 7b showed interesting antifungal activity when tested against Saccharomyces cerevisiae.

[Synthesis and in vitro antimicrobial activity of N-substituted derivatives of phenylpiperidine and phenylpiperazine]. / Sintesi ed attività antimicrobica in vitro di derivati N-sostituiti di fenilpiperidine e fenilpiperazine.

Synthesis and antimicrobial activity of some N-substituted aza- and diaza-phenylcycloalkanes are reported. All the compounds screened in vitro show significant antibacterial and antimycotic activities. Particularly, compounds of the N-(ethoxymethyl)phenylpiperidine series, show activity towards S. aureus 1,2-1,9 superior to ampicillin. Furthermore the microbiological results indicate that the latter activity depends on the position of the phenyl-substituent.