Synthesis of l-carvone-derived imidazo[1,2-a]pyrimidine / nano sodium alginate complexes with significant antifungal activity and sustained releasing performance

Abstract

In search of novel bioactive compounds with significant and broad-spectrum antifungal activity, along with the corresponding complexes with sustained releasing property, a novel series of l-carvone-derived imidazo[1,2-a]pyrimidine compounds 6a ∼ 6t were synthesized, and structurally confirmed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), and high resolution mass spectrum (HRMS). X-Ray single-crystal diffraction analysis was carried out for compound 6h In addition, the antifungal activity of the target compounds was assayed by in vitro test, and the results demonstrated that all the target compounds exhibited antifungal activity against the tested fungi at different levels, in which compound 6b showed outstanding broad-spectrum antifungal activity. An effective and rational three-dimensional quantitative structure-activity relationship (3D-QSAR) model was built to analyze the structure-activity relationship of the target compounds against Physalospora piricola. Furthermore, nanocarrier 8 was synthesized by incorporation of l-carvone moiety into the original skeleton of sodium alginate (SA), and its physicochemical structures were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), FT-IR, X-ray diffraction (XRD), and scanning electron microscope (SEM). It was found that nanocarrier 8 showed a more uneven surface than that of sodium alginate, and an unconsolidated structure with open frameworks. Besides, l-carvone-derived imidazo[1,2-a]pyrimidine/nano sodium alginate complexes were fabricated, and their sustained releasing properties were also evaluated in ethanol/water (1:3, v/v). To our surprise, complex 8/6b-2, which was prepared by the mass ratio of nanocarrier 8 and compound 6b of 3:1, displayed desirable sustained releasing performance when compared with bioactive compound 6b directly thrown into the system, and a well-distributed, compact, and columnar microstructure. Thus, it deserves further study as a promising candidate for the development of nanopesticides.