New Hydroxamic Acid Derivative Prevents Sq-OOH Induced Wrinkle

Abstract

Lipid peroxidation has been suggested to play a key role in damaging biological processes resulting from excessive exposure to UV light. Aging of skin has been associated with increased peroxidation of skin lipid. In particular, squalene, which is a main component of skin surface polyunsaturated lipids, is easily peroxidized. Squalene-monohydroperoxide (Sq-OOH), the initial product of peroxidized squalene, is produced at the human skin by natural exposure to sunlight during day time activities. Recently, a few researchers reported on the damages of hairless mice skin by the topical application of Sq-OOH. Repeated application of Sq-OOH to the hairless mice induced its the skin wrinkles with clear and fine appearance. Histologically were seen, more keratinocyte hypertrophy with Sq-OOH treated skin than with chronic UVB irradiated group in epidermis. In dermis, characteristics, found in UVB irradiated skin, such as the loss of polarity, fractured collagen bundle and elastosis, were not observed severely. The alteration of epidermal layer might be the main factor for the formation of wrinkle caused by Sq-OOH. From the previous works, Sq-OOH is considered as an important source of damage in the early stage of aging process to result in epidermal wrinkle. Thus, it is very important to minimize such damage that would be induced mainly by Sq-OOH against healthy skin condition. Therefore, we tried to develop new anti-aging materials for protecting skin damage by Sq-OOH. Hydroxamic acids, the naturally occurring products exhibit low toxicities in general, and are of interest for many therapeutic applications. Recently, hydroxamic acids and derivatives were reported largely as effective antibacterial and antifungal agents. Their activities originate from their ability to coordinate on metal ions. That is, hydroxamic acid group is regarded as an one electron donor. Hydroxamic acid moiety has also drawn much attention as a reactive oxygen species (ROS) scavenger. In this study, a new skin protecting compound, (4-(Nhydroxycarbamoyl)phenyl)-N-adamantanylcarboxamide (1) is synthesized to show inhibitory activities of lipid peroxidation both in vitro and in vivo. The targeted compound 1 is a hydroxamic acid derivative which possesses an amide linker between hydroxamic acid and adamantane moiety. Adamantane group was adopted as a hydrophobic moiety to optimize antioxidant activity of hydroxamic acid in animal test. Compound 1 is believed to be adequate in skin permeation because of its balance in hydrophilic and hydrophobic character.