Novel S-thiazol-2-yl-furan-2-carbothioate derivatives as potential T3SS inhibitors against Xanthomonas oryzae on rice.

Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is considered as the most destructive disease of rice. Using bactericides is among the widely used traditional methods to control this destructive disease. The excessive and repeated use of the same bactericides is also becoming the reason behind bactericide resistance development. The widely used method for finding the new anti-microbial agents often involves the bacterial virulence factors as a target without affecting bacterial growth. Type III secretion system (T3SS) is a protein appendage and considered as essential virulence factors in most gram-negative bacteria. Due to the conserved construct, T3SS has been regarded as an important mark for the blooming of novel anti-microbial drugs. Towards the search of new T3SS inhibitors, an alternative series of 1,3-thiazole derivatives were designed and synthesized. Their structures were characterized and confirmed by 1H NMR, 13C NMR, MS, and elemental analysis. All the title compounds inhibited the promoter activity of hpa1 gene, significantly. Eight of them showed better inhibition than our previous T3SS inhibitor TS006 (o-coumaric acid, OCA). The treatment of Xoo with eight compounds significantly attenuated HR without affecting bacterial growth. The mRNA levels of some representative genes (hrp/hrc genes) were reduced up to different extents. In vivo bioassay results showed that eight T3SS inhibitors could reduce bacterial leaf blight and bacterial leaf streak symptoms on rice, significantly.