Therapeutics, boronic acid based

Nitric oxide (NO) displays potent activities in the cardiovascular system as well as in the central and peripheral nervous systems. NO and its co-product L-citruUine are produced by the oxidation of L-arginine (28) by nitric oxide synthase (NOS) (Scheme 13.4). Selective modulation of NO biosynthesis offers the opportunity for therapeutic intervention of neurodegenerative diseases, among others. Based on the mechanism proposed for NO biosynthesis, two boronic acid analogues (29 and 30, Figure 13.7) of... 

The use of nanocontainers, such as low-density lipoproteins (LDL) or liposomes is the important approach directed to selective delivery of therapeutics into tumors. One of the observed differences between tumor cells and their normal counterparts is the rate of metabolism of low-density lipoproteins (LDLs). The LDL vesicle comprises a phospholipids/cholesterol shell with a diameter of approximately 15-20 nm, filled with cholesteryl and glyceryl esters of long-chain alkyl carboxylic acids. This difference is based on the increased need that tumor cells possess for cholesterol to facilitate new membrane formation. The overexpression of the LDL receptors on the tumor cell membrane is responsible for its LDL accretion. This provides a basis for cellular differentiation and the targeting of tumor cells with boron if cholesteryl esters of the LDL core are replaced with a boron species that would simulate cholesterol in its physiochanical properties. This concept was proposed by Kahl in the early 1990s. The initial compounds synthesized were esters of carborane carboxylic acid with various fatty acid alcohols [80]. Later, some other derivatives of cholesterol were synthesized [81,82] and LDLs were proposed as tumor delivery agents for carborane-containing porphyrins [83]. 

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