Abstract
Minocycline is a widely used antibacterial agent. Moreover, it is also demonstrated to be effective in several neurodegenerative disorders, due to its antioxidant and anti-inflammatory activities. However, the last activity is only apparent at very high doses. In fact, minocycline poorly crosses the blood-brain barrier (BBB) due to its low lipophilicity and half-life. The present work details the physicochemical characterization of a series of alkanoyl-10-O-minocycline derivatives (2-6), which are able to produce self-assembled aggregates in aqueous solution. The n-octanol/aqueous phase lipophilicity of minocycline and its derivatives were assessed by theoretical calculation, by shake-flask method, and by reversed-phase HPLC. Moreover, we determined their affinity for membrane phospholipids measuring their HPLC retention on phospholipid-based stationary phases, the so-called "Immobilized Artificial Membranes" (IAMs). Our results indicate high lipophilicity values for the minocycline derivatives (compounds 2-6); these values and the corresponding phospholipid affinities increase with the length of the hydrocarbon moiety substituent. Furthermore, the ability of the investigated alkanoyl-10-O-minocycline derivatives to self-assemb...Continue Reading
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