New 2-aryl-6-methyl-3,4-dihydro-β-carbolin-2-iums as potential antifungal agents: Synthesis, bioactivity and structure-activity relationship

Abstract

Thirty new title compounds along with five known analogues were prepared from commercially available 2-arylhydrazin-1-ium chlorides and α-ketoglutaric acid. The mycelium growth rate method was used to evaluate inhibition activity against six strains of plant pathogenic fungi. Most of the compounds displayed the activity for each the fungi at 150 μΜ, higher than azoxystrobin, a positive drug. Compound 6-2 showed the lowest average IC50 value of 4.58 μg/mL for all the fungi where F. solani exhibited the highest susceptibility to most of the compounds. For F. solani, some compounds were more active with IC50 values of 2.67–8.48 μM than thiabendazole (IC50 = 9.30 μM) and/or carbendazim (IC50 = 3.36 μM). The SAR showed that the activity is significantly affected by substituents on the A-ring and/or D-ring along with the degree of unsaturation of the C-ring. Thus, a series of new β-carboline compounds with potent antifungal potential were found.

Simple Analogues of Quaternary Benzo[c]phenanthridine Alkaloids: Discovery of a Novel Antifungal 2-Phenylphthalazin-2-ium Scaffold with Excellent Potency against Phytopathogenic Fungi

“…It was worth mentioning that compared with the analogues A ,− and B , , compound C had more potent activity and a broader antifungal spectrum.…”

“…Based on the understanding of the structure–activity relationships (SARs) of QBAs and with the aim of seeking more potent QBA -like antifungal agents, we previously deigned two classes of structurally simple analogues of QBAs , that is, isoquinoline analogues ( A ) and β-carboline analogues ( B ) (Figure ) by structural simulation. These analogues generally showed similar or even more potent antifungal activity than SA and CH. ,− Besides, the analogues also showed high safety for plant growth . Encouraged by the findings above, herein we further designed a class of novel phthalazine analogues ( C ) (Figure ).…”

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

“…1 H and 13 C NMR spectra were recorded on an Avance III 400 or 500 MHz instrument (Bruker, Karlsruhe, Germany) with trimethylsilane (TMS) as standard and DMSO-d 6 or CD 3 OD as a solvent. Chemical shifts (δ Synthesis of Compound V. According to our previously reported methods, 15,19 the key intermediate V was synthesized from 2-arylhydrazin-1-ium chlorides and 2-oxopentanedioic acid in six steps (Scheme 1). The general procedure is as follows.…”

“…Orange powders; yield: 68%; the melting point and spectral data were consistent with those in the literature. 15 7-Bromine-9-methyl-2-phenyl- 6,9-Dimethyl-2-phenyl-3,4-dihydro-β-carbolin-2-ium bromide (4). Orange powders; yield: 71%; the melting point and spectral data were consistent with those in the literature.…”

“…24,25 The structure−activity relationship (SAR) displayed that the antifungal activity of analogues C (Figure 1) was closely related to the substitution pattern of the D-ring. 15,19 To further explore the substitution pattern of the A-ring on the activity and find promising antifungal candidates, in this research, a series of new 7-chloro-substituted derivatives D (Figure 1) were designed and synthesized as our continuing research. The compounds were tested for inhibition activity in vitro on six strains of important phytopathogenic fungi.…”