A. I. Manzano, F. Medina, F. Pérez-Zúñiga
Feb 24, 2012
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Abstract
Bisphosphonates (BPs) are analogues of pyrophosphate in which the oxygen bridge between the two phosphates is replaced by a methylene group (–CH2–). Substitution of one or both hydrogen atoms of this group by radicals generates a variety of bisphosphonates; usually they are grouped into two types, namely non-N-BP and N-BP, depending on the absence or presence of a nitrogen atom in its molecule, respectively (Russell, 2011). Examples of BPs used in this report are: etidronate and clodronate (non-N-BPs), and pamidronate and alendronate (N-BPs). Bisphosphonates are the leading drug class for the treatment of osteoporosis; as an indication of their usefulness and the spread out of the disease the combined sales of drugs to treat osteoporosis reached $ 6.2 billions in 2004. Besides their application in humans, bisphosphonates are also used for other purposes, mainly as herbicides in plants (Cromartie et al., 1999; Oberhauser et al., 1998), as chemotherapeutic agents (Artz et al., 2008; Docampo & Moreno, 2001; Leon et al., 2006; Moreno & Li, 2008) and in basic research (Rogers et al., 2010; Russell, 2011). The usefulness of bisphosphonates is due to their mechanism of action when they are supplied to the living organism. In fact, they have the ability of interfering with metabolic pathways located at the crossroads of essential processes for life. Some important examples of this crucial role are as follows: a) Bisphosphonates may act as analogs of PP in many of the reactions catalyzed by ligases and some transferases (reaction 1) in which derivatives of the type NRpp-CH2-p are synthesized in the reverse reaction (reaction 2) (Gunther Sillero et al., 2008; Gunther Sillero et al., 2006; Rogers et al., 1996; Russell, 2011).