Design, Synthesis, and Biological Activities of Spirooxindoles Containing Acylhydrazone Fragment Derivatives Based on the Biosynthesis of Alkaloids Derived from Tryptophan

Abstract

On the basis of the biosynthesis of alkaloids derived from tryptophan and considering the wide use of spirooxindole in drug molecular design, a series of novel spirooxindole derivatives containing an acylhydrazone moiety were designed, synthesized, and first evaluated for their biological activities. The results of bioassays indicated that the target compounds possessed good activities against tobacco mosaic virus (TMV); especially compound 4, containing a tert-butyl at the benzene ring, exhibited the best antiviral activity in vitro and inactivation, curative, and protection activities in vivo (48.4%, 58 ± 0.4, 55.2 ± 2.3, and 49.7 ± 1.1% at 500 μg/mL, respectively) compared with ribavirin (38.2, 36.4 ± 0.2, 37.5 ± 0.2, and 36.4 ± 0.1% at 500 μg/mL, respectively) and harmine (44.6, 40.5 ± 0.2, 38.6 ± 0.8, and 42.4 ± 0.6% at 500 μg/mL, respectively). At the same time, these compounds exhibited fungicidal activity selectively against certain fungi; most of these derivatives exhibited >60% fungicidal activity against Physalospora piricola at 50 mg/kg. Additionally, compounds 25 and 14 displayed excellent insecticidal activities (60% motality against C. pipiens pallens at 0.25 mg/kg) even at very low concentrations.

Keywords: acylhydrazone; antiviral activity; biosynthesis; fungicidal activity; insecticidal activity; spirooxindole; tryptophan.