Novel Fungicides Developed from Natural Product Scaffold Show Potent Activity

Researchers have designed and synthesized a series of 45 novel fungicide compounds using the naturally-derived scaffold of chromeno[4,3-b]pyridin-5-one. Characterization and antifungal screening of these derivatives revealed promising activity, particularly against phytopathogenic Alternaria species. 

The chromeno[4,3-b]pyridin-5-one pharmacophore was originally identified in the natural product polynemoraline C. To explore its antifungal potential, investigators attached various ester side chains to the C-7 position. The compounds were fully characterized structurally using NMR and HR-MS. 

Antifungal assays screened the derivatives at 100 μg/mL against Alternaria alternata, Alternaria solani, Botrytis cinerea and Fusarium oxysporum. Most compounds showed enhanced inhibition of Alternaria compared to the other fungal species. The lead compound 1b displayed exceptional activity surpassing the commercial fungicides chlorothalonil and azoxystrobin against both A. alternata and A. solani.

Structure-activity analysis indicated the four-carbon chain length of the C-7 side group strongly influences potency. Selectivity for Alternaria appears dependent on specific ester moieties. The EC50 values for compound 1b were 62.73 and 65.95 μg/mL against A. alternata and A. solani, respectively.

This research demonstrates natural products remain a prime source for developing new agrochemicals. The chromeno[4,3-b]pyridin-5-one scaffold represents a novel antifungal pharamacophore with potential for further optimization as a fungicide. Combating devastating crop pathogens requires continued innovation. Nature’s chemical bounty, when combined with synthetic elaboration, offers promising strategies for designing green pest control solutions.

Further studies should evaluate the mode of action, crop safety and environmental impact of these natural product-inspired fungicides. Their potent Alternaria activity warrants additional hit-to-lead development to produce effective new tools for integrated pest management and sustainable agriculture.