(2-Aminobenzothiazole)-Methyl-1,1-Bisphosphonic Acids: Targeting Matrix Metalloproteinase 13 Inhibition to the Bone

Matrix Metalloproteinases (MMPs) are a family of secreted and membrane-bound enzymes, of which 24 isoforms are known in humans. These enzymes degrade the proteins of the extracellular matrix and play a role of utmost importance in the physiological remodeling of all tissues. However, certain MMPs, such as MMP-2, -9, and -13, can be overexpressed in pathological states, including cancer and metastasis. Consequently, the development of MMP inhibitors (MMPIs) has been explored for a long time as a strategy to prevent and hinder metastatic growth, but the important side effects linked to promiscuous inhibition of MMPs prevented the clinical use of MMPIs. Therefore, several strategies were proposed to improve the therapeutic profile of this pharmaceutical class, including improved selectivity toward specific MMP isoforms and targeting of specific organs and tissues. Combining both approaches, we conducted the synthesis and preliminary biological evaluation of a series of (2-aminobenzothiazole)-methyl-1,1-bisphosphonic acids active as selective inhibitors of MMP-13 via in vitro and in silico studies, which could prove useful for the treatment of bone metastases thanks to the bone-targeting capabilities granted by the bisphosphonic acid group.

Deciphering preferred solid-state conformations in nitrogen-containing bisphosphonates and their coordination compounds. A case study of discrete Cu(ii) complexes based on Cα-substituted analogues of zoledronic acid: crystal structures and solid-state characterization

Conformation diversity of N-containing bisphosphonic acids and related anions within their metal complexes and salts.

COMPLEXES OF SILVER, LEAD, CALCIUM WITH BISPHOSPHONIC LIGANDS

It is interesting in chemical terms and promising in the applied production of new complexes of metals with bisphosphonic ligands with a popular set of consumer properties. To date, little has been studied chemistry of bisphosphonic acid complexes with the basic structure of 1-hydroxymethylene-bisphosphonic acid with a side chain containing 11 carbon atoms and ending with an amino group. The main objective is to obtain new bisphosphonates of s-, p -, d - and f-elements, their characterization by a complex of physical and chemical research methods (NMR and IR spectrometry, RSA, DTA, optical microscopy, laser diffraction) and to identify new applications of bisphosphonic acids and their salts. In the course of the work, complexes of Ag, Pb, Ca, with 1-hydroxymethylene-bisphosphonic acid (H2N(CH2)xC(OH)(H2PO3)2) and its derivatives, the side chain ends with an amino group, its length is 11 carbon atoms. Crystal structures of metal-bisphosphonate complexes with the general formula H2N(CH2)10C(OH)(HPO3)xM (M = Ag, Pb, Ca) were determined. The complexes were characterized by IR spectroscopy and 31P solid-state NMR spectroscopy, RSA. The areas of practical use of the complexes are outlined. It is shown, by the example of wastewater in Kuopio, Finland, that bisphosphonic acids can be used for wastewater treatment of enterprises from heavy metals (M =Pb, Zn, Cd, etc.).