Open AccessHeterocyclic Derivatives of all‐trans Retinoic Acid: in vitro Effects on Fibroblast/Keratinocyte Growth and Differentiation, and in vivo Effects on Guinea‐Pig Skin
Author(s) -
Parnigotto Pier Paolo,
Conconi Maria Teresa,
Bortoletto Chiara,
Manfredini Stefano,
Montesi Francesco,
Schiavon Mariano,
Cancellotti Francesco Maria
Publication year - 1999
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1111/j.1600-0773.1999.tb00066.x
Subject(s) - keratinocyte , retinoic acid , fibroblast , epidermis (zoology) , in vivo , human skin , in vitro , guinea pig , tretinoin , retinoid , hairless , chemistry , biochemistry , biology , microbiology and biotechnology , endocrinology , anatomy , genetics , gene
We investigated the biological effects of five all‐trans retinoic acid derivatives, bearing heterocyclic ring systems in the side chain. Growth assays performed on submerged human fibroblast and keratinocyte cultures revealed that ( E )4‐[2‐(5‐terbuthyl‐thiophen‐2‐yl)propenyl]benzoic acid (compound 5) is the best compound among the studied derivatives for it exibits a weaker antiproliferative activity and induces, like all‐trans retinoic acid does, a significant increase in fibroblast and keratinocyte growth. The morphological and morphometrical analyses of submerged human fibroblast cultures and human epidermis reconstructed in vitro showed that the compound 5 behaves similarly to all‐trans retinoic acid: it induces a decrease in all the cell parameters of submerged fibroblast cultures, and modulates the differentiation of keratinocytes in in vitro reconstructed epidermis. Compound 5 induces thickening of epidermis in vivo , one of the most remarkable pharmacological effects of retinoids on skin, but compared to all‐trans retinoic acid, it induces a weaker irritation on guinea‐pig skin in terms of both erythema and scaling. Compound 5 could then represent a promising candidate for the treatment of certain dermatological diseases.