Trialkylamine Derivatives Containing a Triazole Moiety as Promising Ergosterol Biosynthesis Inhibitor: Design, Synthesis, and Antifungal Activity

Abstract

As a part of our continuing research on amine derivative antifungal agents, 19 novel target compounds containing 1,2,4-triazole and tertiary amine moieties were designed and synthesized, and their in vitro antifungal activities against six phytopathogenic fungi (Magnaporthe grisea, Alternaria solani, Fusarium solani, Curvularia lunata, A. alternata, F. graminearum) were assayed. All target compounds were elucidated by means of 1 H-NMR, 13 C-NMR, high resolution (HR)-MS, and IR analysis. The results showed that most of the derivatives exhibited obvious activity against each of the fungi at 50 µg/mL. Among them, compounds 7f, l, and o displayed excellent activity against A. solani with median effective concentration values (EC 50 ) of 2.88, 8.20, and 1.92 µg/mL. 7o in particular was superior to tebuconazole (EC 50 2.03 µg/mL), a commercial fungicide. Furthermore, compounds 7j, k, and m also showed good activity against F. graminearum with EC 50 values of 11.60, 5.14, and 16.24 µg/mL, and the value of 7k was extremely close to that of tebuconazole (EC 50 3.13 µg/mL). The preliminary analysis of the structure-activity relationship (SAR) demonstrated that combination of the active structure of 1,2,4-triazole with the tertiary amine group containing benzene rings effectively increased the antifungal activities. Generally, introducing halogen atoms obviously improved activities against most of the test fungi to varying degrees, while the presence of OMe decreased the activities. Thus, the results strongly indicate that the newly synthesized derivatives should be lead compounds for the development of novel antifungal agents for the effective control of phytopathogenic fungi.

Antifungal Activity of Osthole on Microsporum canis through Interfering with Biosynthesis of Fungal Cell Wall

“…Besides, the synthetic drugs also possessed certain deficiencies such as a poor curative effect on antifungal therapy [17] . Sensitivity to triazoles became reduced due to the deficiency of AmB binding sites, which could inhibit ergosterol biosynthesis [18] . Polyenes could inhibit the growth of fungi by interacting with ergosterol in cell membrane, but are ineffective on fungus without ergosterol in cell membrane [19] .…”

Novel 1, 2, 4-Triazoles as Antifungal Agents

“…Also, electron-donating groups 59o (Me) or 59p (OMe) considerably reduced the activity. In contrast, the presence of halogen atoms such as 59k (3-F), 59c (4-Cl), (3,4-diCl), and 59n (4-Br) might increase the activity ( Figure 47 ) [ 130 ].…”

Thymol as an Interesting Building Block for Promising Fungicides against Fusarium solani

“…Agricultural inputs, such as fungicides, have been applied and grown significantly in organic farming for the management and control of fungal diseases, especially as a “green revolution” technology . Plant fungal pathogens have relevant impacts on a wide range of crops since several phytopathogenic fungi release prejudicial mycotoxins to animal and human health. − Thus, controlling fungal diseases is essential to keep higher agricultural productivity and minimize monetary losses . Considering the need to develop new fungicides with novel molecular frameworks and mechanisms of action, the agrochemical industry has successfully produced and filled this profitable market.…”