title: Disparate SAR data of griseofulvin analogues for the dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 cancer cells.
abstract: Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes  Trichophyton rubrum  and  Trichophyton mentagrophytes  as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The SAR of the griseofulvin analogues toward the two fungi followed the same trend with the majority being less active than griseofulvin and none had more than twice the potency of the parent compound. A comparison of the antifungal and the anticancer SAR revealed distinct differences, as the majority of analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin in both fungal and mammalian cells, but the differences revealed by this SAR study strongly suggest that the mode-of-action of the compound class toward fungi and mammalian cancer cells is different.
authors.affiliation: Center for Nanomedicine and Theranostics & Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 201, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Mads H
authors.initials: MH
authors.lastname: Rønnest
authors.forename: Marc S
authors.initials: MS
authors.lastname: Raab
authors.forename: Simon
authors.initials: S
authors.lastname: Anderhub
authors.forename: Sven
authors.initials: S
authors.lastname: Boesen
authors.forename: Alwin
authors.initials: A
authors.lastname: Krämer
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Larsen
authors.forename: Mads H
authors.initials: MH
authors.lastname: Clausen
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006118:Griseofulvin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D009172:Mycology / Q000379:methods; D013329:Structure-Activity Relationship; D014249:Trichophyton / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D006118:Griseofulvin