Synthesis and antifungal activity of 2-hydroxy-4,5-methylenedioxyaryl ketones as analogues of kakuol.
In a study aiming to determine the structural elements essential to the antifungal activity of kakuol, we synthesized a series of 2-hydroxy-4,5-methylenedioxyaryl ketones, and we assayed their in vitro antifungal activity. The most sensitive target organisms to the action of these class of compounds were Phytophthora infestans, Phytium ultimum, Cercospora beticola, Cladosporium cucumerinum, and Rhizoctonia solani. Most of the analogs showed a remarkable in vitro activity, and some of them appeared significantly more effective than the natural product. The biological activity was mainly affected by introducing structural modification on the carbonyl moiety of the natural-product molecule. In particular, compound 5a, bearing a C=C bond conjugated to the C=O group, was found active with a MIC value of 10 microg ml(-1) against Cladosporium cucumerinum. The results suggest that 2-hydroxy-4,5-methylenedioxyaryl ketones can be considered promising candidates in the development of new antifungal compounds.
Musso
Loana
L
Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, IT-20133 Milano. loana.musso@unimi.it
Dallavalle
Sabrina
S
Merlini
Lucio
L
Farina
Gandolfina
G
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002963:Cladosporium / Q000187:drug effects; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011427:Propiophenones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000935:Antifungal Agents; D007659:Ketones; D011427:Propiophenones; C049775:kakoul