Some Relations between Chemical Structure and Antifungal Effects of Griseofulvin Analogues

Abstract

SUMMARYInhibitory effects of more than 300 analogues of griseofulvin against six dermatophytic fungi and eight plant pathogenic fungi were determined in an investigation of relations between chemical structure and biological activity. The influence of chemical structure on physical properties of the analogues appeared dominant, but optimum requirements for in vitro performance were somewhat different from those required in vivo for effective control of plant pathogenic or dermatophytic fungi.

Correlation between the in vivo effects of some griseofulvin derivatives and their in vitro interactions with mammalian microtubules

“…This is in agreement with [16,17] obtained on various parasitic fungi. All these compounds induce the same nuclear phenotype on mammalian cells which can be explained by an action on mitotic microtubules [18][19][20][21].…”

Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

“…8 The mode of action is still not determined, but tubulin binding has been proposed. 9,10 More than 400 griseofulvin analogues have been reported since its discovery, and the activity of over 300 of these have been compared with griseofulvin (1) against six dermatophytes in a study by Crosse et al 11 The curling of hyphae in Botrytis allii were also tested, but this phenotype did not correlate with the growth inhibitory effect of the analogues. 11 Griseofulvin analogues with modifications at positions 4, 6, 2′, and 3′ as well as isogriseofulvin analogues with modifications at the 4, 6, 3′, and 4′ positions were tested.…”

“…9,10 More than 400 griseofulvin analogues have been reported since its discovery, and the activity of over 300 of these have been compared with griseofulvin (1) against six dermatophytes in a study by Crosse et al 11 The curling of hyphae in Botrytis allii were also tested, but this phenotype did not correlate with the growth inhibitory effect of the analogues. 11 Griseofulvin analogues with modifications at positions 4, 6, 2′, and 3′ as well as isogriseofulvin analogues with modifications at the 4, 6, 3′, and 4′ positions were tested. No 2′ analogues excelled in growth inhibition of the dermatophytes, 11 but elongation did increase the curling of hyphae with the optimal analogues being 2′-propoxy (46) and 2′-butoxy analogues.…”

“…11 Griseofulvin analogues with modifications at positions 4, 6, 2′, and 3′ as well as isogriseofulvin analogues with modifications at the 4, 6, 3′, and 4′ positions were tested. No 2′ analogues excelled in growth inhibition of the dermatophytes, 11 but elongation did increase the curling of hyphae with the optimal analogues being 2′-propoxy (46) and 2′-butoxy analogues. 12 Most griseofulvin analogues tested showed increased potency against some dermatophytes but exhibiting lower activity against others.…”

“…11 The three compounds were also tested against E. floccosum, M. canis, T. interdigitale, and T. persicolor displaying the same trends, with 17 having lower activity and 45 and 46 retaining the activity of 1.…”