Design and Enantioselective
Synthesis of Chiral Pyranone
Fused Indole Derivatives with Antibacterial Activities against Xanthomonas oryzae pv oryzae for Protection of Rice
posted on 2024-02-22, 16:06authored byKunpeng Teng, Qian Liu, Meng Zhang, Hira Naz, Pengcheng Zheng, Xingxing Wu, Yonggui Robin Chi
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 (3S,4R)-5b, (3S,4R)-5d, and (3S,4R)-5l exhibited promising in vitro efficacy
against Xoo, with EC50 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, EC50 = 27.8 mg/L) and thiodiazole copper (TC, EC50 = 70.1 mg/L). Furthermore, single enantiomer (3S,4R)-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 (3S,4R)-5l and (3R,4S)-5l, wherein
the (3S,4R)-configured stereoisomer
could form a more stable interaction with XooDHPS
(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.