A New Approach for Improving the Antibacterial and Tumor Cytotoxic Activities of Pipemidic Acid by Including It in Trimethyl-β-cyclodextrin.

Abstract

Pipemidic acid (HPPA) is a quinolone antibacterial agent used mostly to treat gram-negative infections of the urinary tract, but its therapeutic use is limited because of its low solubility. Thus, to improve drug solubility, natural cyclodextrins (CDs) are used for their ability of including guest molecules within their cavities. The aim of this work was to evaluate the antibacterial activity and the preliminary anticancer activity of HPPA included into Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) as a possible approach for a new innovative formulation. The inclusion complex of HPPA with TRIMEB was prepared in solid state by the kneading method and confirmed by FT-IR and powered X-ray diffraction. The association in aqueous solutions of pipemidic acid with TRIMEB was investigated by UV-Vis spectroscopy. Job's plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host⁻guest assembly. The antibacterial activity of HPPA, TRIMEB and of their complex was tested on Escherichia coli, Pseudomonas aeruginosa, and Staphilococcus aureus. The complex was able to increase 47.36% of the median antibacterial activity of the free HPPA against E. coli (IC50 = 249 µM vs. 473 µM). Furthermore, these samples were tested on HepG-2 and MCF-7. After 72 h, the median tumoral cytotoxicity exerted by the complex was increased by 78.08% and 94.27% for HepG-2 and MCF-7 respectively, showing a stronger bioactivity of the complex than the single HAPPA.

• Authors: Margherita Lavorgna, Rosa Iacovino, Chiara Russo, Cristina Di Donato, Concetta Piscitelli, Marina Isidori
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 2 (Jan 18 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30669399 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antineoplastic Agents
• beta-Cyclodextrins
• heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin
• Pipemidic Acid

Topics

• Anti-Bacterial Agents (chemistry, pharmacology)
• Antineoplastic Agents (chemistry, pharmacology)
• Bacteria (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Humans
• Microbial Sensitivity Tests
• Molecular Structure
• Pipemidic Acid (chemistry, pharmacology)
• Spectroscopy, Fourier Transform Infrared
• X-Ray Diffraction
• beta-Cyclodextrins (chemistry)