Design and Enantioselective Synthesis of Chiral Pyranone Fused Indole Derivatives with Antibacterial Activities against <i>Xanthomonas oryzae</i> pv <i>oryzae</i> for Protection of Rice
Kunpeng Teng, Qian Liu, Jiqiang Zhang, Hira Naz, Pengcheng Zheng, Xingxing Wu, Yonggui Robin
Abstract
A new class of chiral pyranone fused indole derivatives were prepared by means of N-heterocyclic carbene (NHC) organocatalysis and demonstrated notable antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo) . Bioassays showed that compounds (3 S, 4 R )- 5b, (3 S, 4 R )- 5d, and (3 S, 4 R )- 5l exhibited promising in vitro efficacy against Xoo, with EC 50 values of 9.05, 9.71, and 5.84 mg/L, respectively, which were superior to that of the positive controls with commercial antibacterial agents, bismerthiazol (BT, EC 50 = 27.8 mg/L) and thiodiazole copper (TC, EC 50 = 70.1 mg/L). Furthermore, single enantiomer (3 S, 4 R )- 5l was identified as an optimal structure displaying 55.3% and 52.0% curative and protective activities against Xoo in vivo tests at a concentration of 200 mg/L, which slightly surpassed the positive control with TC (curative and protective activities of 47.2% and 48.8%, respectively). Mechanistic studies through molecular docking analysis revealed preliminary insights into the distinct anti- Xoo activity of the two single enantiomers (3 S, 4 R )- 5l and (3 R, 4 S )- 5l, wherein the (3 S, 4 R )-configured stereoisomer could form a more stable interaction with Xoo DHPS (dihydropteroate synthase). These findings underscore the significant anti- Xoo potential of these chiral pyranone fused indole derivatives, and shall inspire further exploration as promising lead structures for a novel class of bactericides to combat bacterial infections and other plant diseases.