Novel locally active estrogens accelerate cutaneous wound healing. A preliminary study.
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.
Brufani
Mario
M
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
Ceccacci
Francesca
F
Filocamo
Luigi
L
Garofalo
Barbara
B
Joudioux
Roberta
R
La Bella
Angela
A
Leonelli
Francesca
F
Migneco
Luisa M
LM
Bettolo
Rinaldo Marini
RM
Farina
Paolo M
PM
Ashcroft
Gillian S
GS
Routley
Claire
C
Hardman
Matthew
M
Meda
Clara
C
Rando
Gianpaolo
G
Maggi
Adriana
A
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*
D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol