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

Abstract

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.

Experimental synthesis, biological evaluation, theoretical investigations of some novel benzoxazolinone based Schiff under eco-environmental conditions as potential antioxidant agents

“…[11] Furthermore, these compounds have gained considerable attention in the field of medicinal chemistry due to their role in many biological activities, including anti-inflammatory, [12] antioxidant, [13] antifungal, [14,15] antibacterial and antiviral, [16] anticancer, [17] antiparasitic, [18] herbicidal, [19] as well as chelating agents. [20,21] However, an additional bioactive functionalized moiety in the bisphosphonate molecule such as 1H-indazole, 1Hpyrazolo [3,4-b]pyridine and 1H-pyrazolo [3,4-b]quinolone, [22] 2amino-benzothiazole, [23] nitrogen and sulfur, [24] sulfonylamino, [25] fluoro-substituted amine, [26] pyrazole, [27] acrylamide-derived monomer, [28] amino acid, [29] hyaluronic acid, [30] and ethylidene-pyridine bisphosphonate polyoxovanadates complexes, [31] give new derivatives for this class of molecules and offer promising and remarkable biological and industrial applications.…”

One‐Pot Microwave‐Assisted Synthesis, in Vitro Anti‐inflammatory Evaluation and Computer‐Aided Molecular Design of Novel Sulfamide‐Containing Bisphosphonates Derivatives

“…However, an additional bioactive functionalized moiety in the bisphosphonate molecule such as 1H‐indazole, 1H‐pyrazolo[3,4‐b]pyridine and 1H‐pyrazolo[3,4‐b]quinolone, [22] 2‐amino‐ benzothiazole, [23] nitrogen and sulfur, [24] sulfonylamino, [25] fluoro‐substituted amine, [26] pyrazole, [27] acrylamide‐derived monomer, [28] amino acid, [29] hyaluronic acid, [30] and ethylidene‐pyridine bisphosphonate polyoxovanadates complexes, [31] give new derivatives for this class of molecules and offer promising and remarkable biological and industrial applications.…”

“…[11] Furthermore, these compounds have gained considerable attention in the field of medicinal chemistry due to their role in many biological activities, including anti-inflammatory, [12] antioxidant, [13] antifungal, [14,15] antibacterial and antiviral, [16] anticancer, [17] antiparasitic, [18] herbicidal, [19] as well as chelating agents. [20,21] However, an additional bioactive functionalized moiety in the bisphosphonate molecule such as 1H-indazole, 1Hpyrazolo [3,4-b]pyridine and 1H-pyrazolo [3,4-b]quinolone, [22] 2amino-benzothiazole, [23] nitrogen and sulfur, [24] sulfonylamino, [25] fluoro-substituted amine, [26] pyrazole, [27] acrylamide-derived monomer, [28] amino acid, [29] hyaluronic acid, [30] and ethylidene-pyridine bisphosphonate polyoxovanadates complexes, [31] give new derivatives for this class of molecules and offer promising and remarkable biological and industrial applications.…”