Design, synthesis and bioactivity of benzimidazole-2-carbamates as soil-borne anti-fungal agents

Worldwide, fungi pathogens considered to be a lead cause of loss for vegetable crop production. Although, several strategies have been used to manage soil borne fungal diseases, however, higher percentage of the loss of crop production is that caused by fungal pathogens especially in Oman. Management of Pythium-induced diseases of cucumber has relied on the use of imported fungicides, biological control and cultural practices. Mefenoxam and hymexazol are two common fungicides for the management of Pythium-induced diseases in Oman. Despite their use in different farms, mefenoxam suffers from rapid biodegradation in soil while resistance has been reported among Pythium species to hymexazol. Thus, in this work we proposed a methodology of preparing a series of 2-carbamate benzimidazole derivatives of potential antifungal activity and use it against the fungal pathogens that cause the most loss of vegetables crop production in Oman.

Benzimidazole scaffolds have been widely used in medicinal chemistry and drug development due to their numerous medical and biological activities. Methyl benzimidazole-2-yl-carbamate (MBC) in particular is a well-known building block found in many fungicidal drugs in agriculture field.

Seventeen benzimidazole derivatives were synthesized in multistep reactions with acceptable yields. Structures of all newly synthesized compounds were identified and characterized using 1H-NMR, IR, HRMS, and melting point. Final compounds were tested on five soil-borne pathogens. Results of bioassays showed some compounds significantly affected the growth of Pythium aphanidermatum, a serious pathogen of vegetable crops worldwide. At least one class of these derivatives was the most efficacious, which resulted in 96% growth inhibition in Pythium at 100 mg L-1.