New melanin biosynthesis inhibitors and their structural similarities

Abstract

AbstractRelationships between their activities as blast control agents, and their abilities to inhibit mycelial melanisation on a nutrient agar, are described for 103 substituted benzothiazol‐2(3H)‐ones, benzoxazol‐2(3H)‐ones, indolin‐2‐ones, quinolin‐2(1H)‐ones, 1,2,3,4‐tetrahydroquinolin‐2‐ones, benzo‐1,4‐thiazin‐3(2H)‐ones and benz‐1,4‐oxazin‐3(2H)‐ones, and some corresponding thiones. Several compounds in the respective series had a high protective activity and an antimelanisation activity against the blast fungus Pyricularia oryzae; furthermore, there was a good correlation in both of these activities, indicating that these compounds belong to the group of melanin biosynthesis inhibitors. Structural similarities of these compounds can be identified as follows: (a) having a benzo‐bicyclic ring system; (b) containing a nitrogen atom in one ring at a position alpha to the benzene ring system; and (c) substitution, at the ring nitrogen atom, at the peri position in the aromatic ring relative to the nitrogen atom, and at the position alpha to the nitrogen atom in the ring system, with a double bond such as in carbonyl and thiocarbonyl groups. Among the compounds that have been proposed as melanin biosynthesis inhibitors, the chemical structures of tricyclazole, pyroquilon, 4,5‐dihydro‐4‐methyltetrazolo[1,5‐a]quinazolin‐5‐one (PP‐389), [1,2,4]‐triazolo[4,3‐a]quinoline and 1‐methylquinolin‐2(1H)‐one exhibit the structural similarities described above; however, 4,5,6,7‐tetrachlorophthalide, 2,3,4,5,6‐pentachlorobenzyl alcohol and N‐substituted‐2,3,4,5‐tetrachloro‐6‐(hydroxymethyl)benzamides do not have such similarities in their chemical structures.