title: Novel locally active estrogens accelerate cutaneous wound healing. A preliminary study.
abstract: New 17beta-estradiol (E2) derivatives 1-11 were synthesized from an estrone derivative by addition of organometallic reagents prepared from protected alpha,omega-alkynols and further elaboration of the addition products. The estrogenic activity of these novel compounds was determined using in vitro binding competition assay and transactivation analysis. Among the E2 derivatives synthesized, compound 2 showed the highest transactivation potency and was therefore tested for its ability to modulate cutaneous wound healing in vivo. Compound 2's ability to accelerate wound healing in ovariectomized mice and decrease the production of inflammatory molecules was comparable to that of E2. However, the activity of compound 2 was not superimposable to E2 with regard to the cells involved in the wound repairing process. When locally administered, compound 2 did not show any systemic activity on ER. This class of compounds with clear beneficial effects on wound healing and suitable for topical administration may lead to the generation of innovative drugs for an area of unmet clinical need.
authors.affiliation: Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Università degli Studi di Roma "La Sapienza", via degli Apuli 9, I-00185 Roma, Italy. mario.brufani@uniroma1.it
authors.forename: Mario
authors.initials: M
authors.lastname: Brufani
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccacci
authors.forename: Luigi
authors.initials: L
authors.lastname: Filocamo
authors.forename: Barbara
authors.initials: B
authors.lastname: Garofalo
authors.forename: Roberta
authors.initials: R
authors.lastname: Joudioux
authors.forename: Angela
authors.initials: A
authors.lastname: La Bella
authors.forename: Francesca
authors.initials: F
authors.lastname: Leonelli
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Migneco
authors.forename: Rinaldo Marini
authors.initials: RM
authors.lastname: Bettolo
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Farina
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Ashcroft
authors.forename: Claire
authors.initials: C
authors.lastname: Routley
authors.forename: Matthew
authors.initials: M
authors.lastname: Hardman
authors.forename: Clara
authors.initials: C
authors.lastname: Meda
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Rando
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D004958:Estradiol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol