## 3 Synthetic Coumarin Derivatives in Plant Protection
A structure-activity relationship analysis revealed the following conclusions: the replacement of the amide bond with a hydrazide bond led to an increase in antifungal activity; derivatives with an amide bond showed better activity against _B. cinerea_ and _R. solani_, compounds with electron-withdrawing groups had no effect on _A. cucumerina_; chlorinated and fluorinated phenylhydrazine derivatives were effective against _C. anthrax_. Sodium 3-hydroxycoumarin (Figure 6), inhibited a causal agent of witches' broom disease in _Theobroma cacao_ L., _Moniliophthora pernicosa_ fungus [33]. Copper (II) complex with coumarins, [L\({}_{2}\)Cu(OAc)], have showed strong inhibition against both, pathogen fungi _Alternaria alternata_, and Gram-positive bacteria (_Bacillus subtilis_). The activity of this complex was based on the leakage of sugars and electrolytes from microbial cells accompanied by collapsed hyphae of _A. flavus_ and membrane blebbing of _B. subtilis_[118]. In study of [PERSON] et al. [119], 40 coumarins were tested against the most economically important phytopathogenic fungi _Fusarium solani_. The most potent inhibitors of fungal growth were 6-nitrocomarin (Figure 6) among the monosubstituted coumarins and natural prenylated coumarin, 7-hydroxy-8-prenylcoumarin or osthenol (Figure 6) (with a minimal inhibitory concentration (MIC) of 125 \(\upmu\)g/mL, both). A series of synthesized 8-substituted coumarin derivatives exhibited moderate to high antifungal activity against four phytopathogenic fungi: _Botrytis cinerea_, _Colletotrichum gloeosporoides_, _Fusarium oxysporum_, and _Valsa mali_. The strongest fungal inhibition has been demonstrated by 8-chloro coumarin and ethyl 8-chloro-coumarin-3-carboxylate (Figure 6) [34]. Study of [PERSON] et al. has shown that 7-substituted-coumarinly thiosemicarbazides possess a better antifungal activity than 4-substituted ones against mycotoxin producer, _Aspergillus flavus_ Link [120].. The 38 simple coumarin derivatives were synthesized in environmentally safe organic solvents [121], and their antifungal activities were assayed on four cultures of phytopathogenic fungi (_Fusarium oxysporum_ f. sp. _Iyocpersici_, _Fusarium culmorum_, _Macrophomina phaseolina_, and _Sclerotinia sclerotium_). In order to validate their environmental impact, the compounds were assessed against soil-beneficial nematodes and bacteria. Coumarin derivative, which possesses 3-CN and 6-OH groups at the coumarin scaffold, has shown antifungal activities against all fungi tested, is nontoxic, and is not harmful to beneficial bacteria and nematodes [35]. Coumarinly Schiff bases proved to be promising candidates for inhibition of _M. phaseolina_, especially derivatives with an aromatic nucleus substituted with a bromine atom (71.51% inhibition), or a methoxy group (70.36% inhibition) (Figure 7). Also, neither compound exhibited inhibitory effects against two beneficial bacteria (_Bacillus mycoides_ and _Bradyrhizobium japonicum_) and two entomopathogenic nematodes (_Heterohndditis bacteriophora_ and _Steinernema feltiae_) [36]. Among the novel series of 4-methylumbelliferone derivatives, coumarin esters exhibited significant inhibitory activity against _Botrytis cinerea_, especially those without hydroxyl groups. A phenolic aldehyde with hydroxyl group in ortho position had showed the most effective activity against _Fusarium oxysporum_ f. sp. _Iyocpersici_[122]. Coumarin derivatives synthesized using Bronsted acidic pyridinium-based ionic liquid displayed antifungal activities against _M. phaseolina_ comparable to reference fungicide mancozeb [123]. Plant pathogenic bacteria invade host plants through root wounds, and colonize and multiply profusely in living plant tissues. Disease symptoms are pretty characteristic of the pathogen/host combination, but infection is usually followed by wilting and death of the host plant. Infection reduces plant growth and yield and lowers product quality.