New 7-Chloro-9-methyl-2-phenyl-3,4-dihydro-β-carbolin-2-iums as Promising Fungicide Candidates: Design, Synthesis, and Bioactivity

As our further research, a series of new 7-chloro-9-methyl-2-phenyl-3,4-dihydro-beta-carbolin-2-iums were designed and synthesized. Twelve compounds were found with excellent inhibition activity in vitro on three to five out of six phytopathogenic fungi, superior to standard drugs thiabendazole and/or azoxystrobin. Especially, 18 displayed the highest activity against three out of the fungi and the highest comprehensive activity for all of the fungi. The test in vivo revealed that 18 at 50 mu g/mL was able to completely control Physalospora piricola infections in apples over 8 days. Scanning/transmission electron microscopic observations found that 18 could damage the hyphal integrity and cell membrane structure of P. piricola. The safety evaluation showed that 18 had no effect on the germination rate of cowpea seed at <= 200 mu g/mL. The SAR revealed that the combination of 7-Cl and 2'- or 4'-alkyl is conducive to improvement of the activity. Thus, 7-chloro-9-methyl-2-phenyl-3,4-dihydro-beta-carbolin-2-ium is a promising antifungal lead scaffold.