Photodegradation of the antibacterial, antifungal and antiprotozoal drug candidate 2-(2-nitrovinyl) furan (G-0) in solid inclusion complexes with β-cyclodextrin derivatives: Characterization by NMR spectroscopy and in silico toxicity screening

Abstract

This work aimed to evaluate the effect of inclusion complex (IC) formation between the drug candidate 2-(2-nitrovinyl) furan (G-0) and hydroxypropyl β-cyclodextrin (HP-β-CD) or sulfobutylether β-cyclodextrin (SBE-β-CD) on the drug's photostability under light exposure. Freeze-dried cyclodextrin inclusion complexes (ICs) and their corresponding physical mixtures were subjected to standardized forced irradiation and light exposure conditions according to ICH guidelines. Kinetic analysis suggested potential alterations in photodegradation pathways. The HPLC chromatographic profile of the ICs exhibited a distinct impurity pattern compared to the physical mixtures, while the profiles of the two ICs were similar. The main photodegradation product (PD1) was identified with a retention time of 5.4 min and a maximum absorption wavelength (λ_max) of 330 nm. PD1 was isolated using High-Performance Liquid Chromatography with diode array detection (HPLC-DAD) and further characterized through Nuclear Magnetic Resonance (NMR) spectroscopy. Combining 1D (¹H NMR, ¹³C {¹H}) and 2D (COSY, HSQC and HMBC) NMR measurements revealed the presence of two substances in equilibrium, identified as (2Z,4Z)-5-nitropenta-2,4-dienoic acid (NPDA) and its corresponding salt. The hazard classification of NPDA was assessed following ICH M7 guidelines using QSAR and expert rule-based toxicity screening methods, providing insights into its potential risk profile.