Design, Synthesis, Characterization, and Biological Activities of Novel Spirooxindole Analogues Containing Hydantoin, Thiohydantoin, Urea, and Thiourea Moieties

Abstract

On the basis of the scaffolds widely used in drug design, a series of novel spirooxindole derivatives containing hydantoin, thiohydantoin, urea, and thiourea moieties have been designed, synthesized, characterized, and first evaluated for their biological activities. The diastereoselectivity mechanism is proposed, and the systematic conformational analysis is performed. The bioassay results show that the target compounds possess moderate to good antiviral activities against tobacco mosaic virus (TMV), among which compound <b>22</b> shows the highest antiviral activity <i>in vitro</i> as well as inactivation, curative, and protection activities <i>in vivo</i> (45 ± 1, 47 ± 3, 50 ± 1, and 51 ± 1%, 500 mg/L, respectively), higher than ribavirin (38 ± 1, 36 ± 1, 38 ± 1, and 36 ± 1%, 500 mg/L, respectively). Thus, compound <b>22</b> is a promising candidate for anti-TMV development. Most of these compounds show broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi and selective fungicidal activities against <i>Physalospora piricola</i>, <i>Sclerotinia sclerotiorum</i>, and <i>Rhizoctonia cerealis</i>. Additionally, some of these compounds exhibit insecticidal activity against <i>Culex pipiens pallens</i>, <i>Mythimna separata</i>, <i>Helicoverpa armigera</i>, and <i>Pyrausta nubilalis</i>. Compound <b>17</b> exhibits the highest larvicidal activity (LC₅₀ was 0.32 mg/L) against <i>C. pipiens pallens</i>.