Supramolecular complex of norfloxacin and sulfamethoxazole: Synthesis, characterization, and evaluation of the antibacterial activity

Fluorquinolones (FQs) and sulfonamides (SAs) are antibacterial compounds widely used in therapeutics. The combination of antibacterials is a strategy commonly employed to overcome resistance and to improve pharmacokinetic properties. So, the aims of this study were to design, prepare and characterize a multicomponent solid formed by the FQ norfloxacin (NOR) and the SA sulfamethoxazole (SMX), and to evaluate the in vitro antibacterial activity of their combinations. SMX and NOR were ground with acetonitrile. The obtained solid was analyzed by melting point (m.p), ¹H NMR, hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetry, powder X-ray diffraction (PXRD) and DRIFT.¹ The antibacterial effect of NOR, SMX and NOR-SMX was evaluated against Escherichia coli ATCC 25922 using the macrodilution method and checkerboard. The minimum inhibitory concentration (MIC) and the fractional inhibitory concentration (CIF) were determined.² The solid obtained showed m.p. and DSC extrapolated onset temperatures different from NOR or SMX, and both components were present in the solid in a 1:1 ratio. The PXRD patterns demonstrated that NOR and SMX form a new solid phase. Results of the checkerboard method showed synergistic effect, with a FIC index of 0.40.³ These results are very promising and we continue developing new biopharmaceutical assays.

References:

1. Pinto Vitorino, G.; Sperandeo, N. R.; Caira, M.; Mazzieri, M. R. Crystal Growth & Design, 13: 1050-58. 2013.
2. Eliopoulos GM, Moellering Jr RC. Antimicrobial combinations. En: Lorian V, editor. Antibiotics in laboratory medicine, 4 ed. Baltimore, Md: The Williams & Wilkins Co. 1996.
3. Pinto Vitorino G, Becerra MC, Barrera GD, Caira MR, Mazzieri MR. Biological and Pharmaceutical Bulletin, 2017, 40, 758–764.