Quinazoline Alkaloids for Plant Protection: Design, Synthesis, and Biological Evaluation of Novel Deoxyvasicinone Derivatives

Abstract

For many years, plant diseases brought about by viruses plus fungi have led to significant declines in crop yield as well as quality, highlighting the urgent need for the development of effective antiviral as well as fungicidal agents. Quinazolinone alkaloids have an important role in drug research and development (R&D). Herein, alkaloid deoxyvasicinone was chosen as the mother structure; deoxyvasicinone derivatives were designed, prepared, and evaluated for their antiviral and antifungal activities. The antiviral activity against tobacco mosaic virus (TMV) suggested most compounds displayed better inhibitory effects compared to ribavirin; especially, compounds 3a, 3d, 4, and 5 with significantly higher antiviral activities (AAs) (EC₅₀ values: 113–208 μg/mL) than ningnanmycin (EC₅₀ value: 229 μg/mL) emerged as novel antiviral leads. Compound 4 was chosen for the antiviral action mechanism study, which suggested that it can interfere with the formation of 20S coat protein (CP) discs, thereby affecting the TMV particles’ assembly. In vitro antifungal activity research suggested most compounds exhibited wide-spectrum fungicidal activities (FAs) at a test concentration of 50 μg/mL. Further pesticide-likeness research exhibited that compounds 3a, 3d, 4, and 5 showed pesticide-likeness with the potential to be developed as pesticide candidates. This research establishes a basis for the use of deoxyvasicinone alkaloids in green pesticides.