title: Enhanced solubility and antibacterial activity of lipophilic fluoro-substituted N-benzoyl-2-aminobenzothiazoles by complexation with β-cyclodextrins.
abstract: 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 β-CD and one of FDA/EMA approved CDs for parenteral use (i.e. HP-β-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 β-CD and HP-β-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.
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Trapani
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: N
authors.initials: N
authors.lastname: De Laurentis
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Armenise
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Carrieri
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Defrenza
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rosato
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Mandracchia
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi di Pavia, viale Taramelli, 12, 27100 Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tripodo
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Salomone
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Capriati
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Franchini
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona, 4, I-70125 Bari, Italy. Electronic address: filomena.corbo@uniba.it.
authors.forename: F
authors.initials: F
authors.lastname: Corbo
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology*; D003198:Computer Simulation; D005079:Excipients / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D012995:Solubility; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D052160:Benzothiazoles; D005079:Excipients; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005461:Fluorine
keywords: 2-Hydroxypropyl-b-cyclodextrin (PubChem CID: 44134771); Antimicrobial agents; Cyclodextrins; Molecular; Norfloxacin (PubChemCID: 4539); Nuclear magnetic resonance; modelling; β-Cyclodextrin (PubChem CID: 444041)