Discovery of Novel Quinazoline-2-Aminothiazole Hybrids Containing a 4-Piperidinylamide Linker as Potential Fungicides against the Phytopathogenic Fungus .

A total of 29 novel quinazoline-2-aminothiazole hybrids containing a 4-piperidinylamide linker were designed, synthesized, and evaluated for their anti-microbial properties against phytopathogenic fungi and bacteria of agricultural importance. The anti-fungal assays indicated that some of the target compounds exhibited excellent inhibitory effects in vitro against . For example, 11 compounds within this series (including , , , , , , , , , , and ) were found to possess EC values (effective concentration for 50% activity) ranging from 0.42 to 2.05 μg/mL against this pathogen. In particular, compound with a 2-chloro-6-fluorophenyl substituent displayed a potent anti- efficacy with EC = 0.42 μg/mL, nearly threefold more effective than the commercialized fungicide Chlorothalonil (EC = 1.20 μg/mL) and also slightly superior to the other fungicide Carbendazim (EC = 0.53 μg/mL). Moreover, compound could efficiently inhibit the growth of in vivo on the potted rice plants, displaying an impressive protection efficacy of 82.3% at 200 μg/mL, better than those of the fungicides Carbendazim (69.8%) and Chlorothalonil (48.9%). Finally, the mechanistic studies showed that compound exerted its anti-fungal effects by altering the mycelial morphology, increasing the cell membrane permeability, and destroying the cell membrane integrity. On the other hand, some compounds demonstrated good anti-bacterial effects in vitro against pv. (). Overall, the presented results implied that 4-piperidinylamide-bridged quinazoline-2-aminothiazole hybrids held the promise of acting as lead compounds for developing more efficient fungicides to control .