Hair Loss Study Abstract: A minoxidil-related compound lacking a C6 substitution still exhibits strong anti-lysyl hydroxylase activity in vitro.
|
Title
A minoxidil-related compound (Aminexil) lacking a C6 substitution still exhibits
strong anti-lysyl hydroxylase activity in vitro.
Author
Mahé YF; Buan B; Bernard BA
Address
Hair Biology Research Group, L'Oréal, Centre de Recherche C.Zviak, Clichy, France.
Source
Skin Pharmacol, 9(3):177-83 1996
Abstract
It has been previously reported that minoxidil inhibits the activity of
lysyl hydroxylase (LH), an enzyme which catalyzes the formation of hydroxylysine, which is
necessary for proper maturation of collagen at the transcriptional and enzymatic levels.
Using the reverse transcriptase-polymerase chain reaction, we confirmed that this
inhibition occurred at least at the transcriptional level. Furthermore, we took advantage
of this sensitive and rapid method to perform a quantitative structure activity relation
study using several compounds structurally related to minoxidil. We found
that when the C6 of the pyrimidinyl moiety was substituted, it had to be by a tertiary
nitrogen, i.e. an N-piperidin ring for the inhibition of LH mRNA synthesis to be observed.
Surprisingly, however, we found that 2,4-diamino-pyrimidin-3-oxide (Aminexil), a new compound lacking
an organic moiety para to the nitroxide oxygen, also retained a high inhibitory effect on
LH mRNA expression, comparable to that of minoxidil. We thus conclude that
the presence of a substituent para to the nitroxide oxygen is dispensable for inhibition
of LH mRNA to be observed in vitro. This brings new insights into the design of
therapeutic agents useful in any condition where an overproduction of mature collagen is
unwanted, i.e. accelerated wound healing, keloids and localized scleroderma.
Language
Eng
Unique Identifier
96354338 |
