Design, synthesis, antifungal activity, and 3D-QSAR of coumarin derivatives

Abstract

In our research, a series of 8-substituted coumarin derivatives were synthesized, and their structures were confirmed by FT-IR, 1 H-NMR, and MS (or HRMS). In activity screening, the synthesized compounds exhibited potent antifungal activity against 4 phytopathogenic fungi: Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium oxysporum, and Valsa mali. Notably, 8-chloro coumarin and ethyl 8-chloro-coumarin-3-carboxylate showed the strongest fungus inhibition with EC 50 of 0.085 and 0.078 mmol/L against V. mali. Furthermore, 3D-QSAR models (CoMFA and CoMSIA) of the title compounds against V. mali were established on the basis of their antifungal activities. The results indicated that the appropriate small, hydrophilic and electron-withdrawing groups on coumarin's C-3 and C-8, respectively, could enhance the antifungal activity. The information obtained will be very helpful for designing new derivatives with high antifungal activities.

Biological Activities Related to Plant Protection and Environmental Effects of Coumarin Derivatives: QSAR and Molecular Docking Studies

“…Song et al [ 8 ] stressed the importance of bromine as substituents for higher antifungal activity. A 3D-QSAR study of Wei et al [ 9 ] relieved that small electron-withdrawing substituents of coumarin’s phenyl ring and hydrophilic electron-donating groups on the coumarin’s pyrone ring could enhance the antifungal activity. Moreover, 4-methyl coumarin with benzoyl group at the C-7 position has the only one that showed significant activity against Fusarium solani among the other compounds [ 60 ].…”

“…Coumarins, secondary plant metabolites and their derivatives, demonstrated a wide range of biological activities on different organisms (invertebrate pests, pathogenic fungus and other microorganisms and weeds), as well as their applications in agriculture as ecofriendly plant protection agents. Several coumarin derivatives have been reported as strong antifungal agents against Sclerotinia sclerotiorum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium oxysporum, Valsa mali and Moniliophthora perniciosa [8][9][10]. Coumarins also have antimicrobial potential against phytopathogens: Ralstonia solanacearum [11], Agrobacterium tumefaciens [12], Pseudomonas aeruginosa [13,14].…”

Ultrasound-Assisted Synthesis, Antifungal Activity against Fusarium oxysporum, and Three-Dimensional Quantitative Structure–Activity Relationship of N,S-Dialkyl Dithiocarbamates Derived from 2-Amino Acids

“…7 Several examples of CoMFA models for the discovery/design/development of antifungals against phytopathogens can be found in available publications with successful results comprising different scaffolds/moieties. 5,6,8−10…”

Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi, the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action

“…Coumarins, secondary plant products and their synthetic derivatives, demonstrated a wide range of biological activities on different organisms (invertebrate pests, pathogenic fungus and other microorganisms and weeds). Several coumarin derivatives have been reported as strong antifungal agents against Sclerotinia sclerotiorum , Botrytis cinerea , Colletotrichum gloeosporioides , Fusarium oxysporum , Valsa mali and Moniliophthora perniciosa [ 7 , 8 , 9 ]. Coumarins also have antibacterial potential against phytopathogens: Ralstonia solanacearum [ 10 ], Agrobacterium tumefaciens [ 11 ], and Pseudomonas aeruginosa [ 12 ].…”