Synthesis of new 4-aryloxy-N-arylanilines and their inhibitory activities against succinate-cytochrome c reductase

Abstract

Succinate-cytochrome c reductase (SCR) is composed of a mixture of mitochondrial complex II (succinate-ubiquinone oxidoreductase) and complex III (cytochrome bc₁ complex). Meanwhile, complexes II and III are two promising targets of numerous antibiotics and fungicides. With an aim to identify new lead structures for SCR, complex II or III, a new series of 4-aryloxy-N-arylanilines were synthesized by introducing a 4-aryloxy phenyl group as one of the aryl groups in diaryl amines. With the economic Cu(OAc)₂·H₂O as the optimal copper promoter, a simple and facile protocol was utilized to afford 24 target products in 56-93% yields. Furthermore, extensive screening results suggested variable inhibitory activities of these compounds against SCR. Exceptionally, compounds 7k-7n showed excellent inhibition potency with their IC₅₀ values in the nanomolar range, demonstrating higher potency than the commercial controls (penthiopyrad and azoxystrobin) by over one order of magnitude.

Keywords: 4-Aryloxy-N-arylanilines; Inhibitory activities; Mitochondrial complex II; Mitochondrial complex III; Succinate-cytochrome c reductase (SCR); Synthesis.