Design, synthesis and biological evaluation of trinary benzocoumarin-thiazoles-azomethines derivatives as effective and selective inhibitors of alkaline phosphatase
“…Inhibitors of ALP showed great potential as i) drugs for the treatment of diseases related to pyrophosphate metabolism disorders, [112] chronic kidney diseases, [113] renovascular hypertension, [114] or cancer; [115] ii) probes for fluorescence imaging of ALP in live cells or tissues. [116] ALP inhibitors such as (-)-p-bromotetramisole, 3-isobutyl-1-methylxanthine, theophylline, and vanadate were shown to activate cystic fibrosis transmembrane conductance regulator (CFTR) ion channel and could be used to increase the efficacy of cystic fibrosis (CF) therapy.…”
Since the 1960s the membrane-bound enzyme alkaline phosphatase (ALP) has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even from the surface of nanocarriers, this enzyme enables the design of drug delivery systems that can alter their properties in the body on demand. Anionic nanocarriers exhibiting bioinert properties can alter their surface to interactive once having reached the target site as due to an ALP-triggered cleavage of anionic phosphate groups from their surface charge converts to cationic improving for instance cellular uptake. Moreover, features such as the accumulation of nanocarriers at the target site or a targeted drug release triggered by ALP can be introduced. In addition, ALP is utilized to improve the potential of numerous diagnostic systems. Within this review, one provides an overview about the activity, selectivity, and distribution of this enzyme, as well as the great variety of applications in drug delivery and diagnostics making use of it.
“…Inhibitors of ALP showed great potential as i) drugs for the treatment of diseases related to pyrophosphate metabolism disorders, [112] chronic kidney diseases, [113] renovascular hypertension, [114] or cancer; [115] ii) probes for fluorescence imaging of ALP in live cells or tissues. [116] ALP inhibitors such as (-)-p-bromotetramisole, 3-isobutyl-1-methylxanthine, theophylline, and vanadate were shown to activate cystic fibrosis transmembrane conductance regulator (CFTR) ion channel and could be used to increase the efficacy of cystic fibrosis (CF) therapy.…”
Since the 1960s the membrane-bound enzyme alkaline phosphatase (ALP) has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even from the surface of nanocarriers, this enzyme enables the design of drug delivery systems that can alter their properties in the body on demand. Anionic nanocarriers exhibiting bioinert properties can alter their surface to interactive once having reached the target site as due to an ALP-triggered cleavage of anionic phosphate groups from their surface charge converts to cationic improving for instance cellular uptake. Moreover, features such as the accumulation of nanocarriers at the target site or a targeted drug release triggered by ALP can be introduced. In addition, ALP is utilized to improve the potential of numerous diagnostic systems. Within this review, one provides an overview about the activity, selectivity, and distribution of this enzyme, as well as the great variety of applications in drug delivery and diagnostics making use of it.
“…In recent years, several inhibitors of APs based on biaryl sulfonamide, chromone, triazole and coumarin sulfonate motifs have been reported. [25][26][27][28][29][30][31][32] APs have become important target enzymes owing to their considerable pharmacological importance in medicinal chemistry. 33,34a,b Some compounds were found to be effective inhibitors of AP, but most of them inhibited APs non-selectively.…”
Aurones are the plant secondary metabolites belonging to the flavonoid’s family. The bioactivities of aurones are very promising, thus these heterocyclic compounds can be considered as an alluring scaffold for drug design and development.
“…In addition, they showed modest antiproliferative activity against HeLa and MCF‐7 cancer cell lines (less than 70% inhibition at 100 μM concentration). [ 86 ] …”
Alkaline phosphatases are found in different living species and play crucial roles in various significant functions, such as hydrolyzing a variable spectrum of phosphatecontaining physiological compounds, contributing to DNA synthesis, bone calcification, and attenuation of inflammation. They are homodimeric enzymes; each subunit contains one magnesium ion and two zinc ions crucial for the catalytic activity of the enzyme. Alkaline phosphatases exist in four distinct isoenzymes (placental, intestinal, germ cell, and tissue nonspecific alkaline phosphatases), which are expressed by four different genes; each one of them has distinguished functions. Any disturbance in the gene expression of alkaline phosphatase eventually induces serious disease conditions. Thus, the need to explore new lead inhibitors has increased recently. In this literature review, we aim to investigate the role of alkaline phosphatase in different diseases and physiological conditions and to study the structure-activity relationships of recently reported inhibitors. We focused on the lead compounds reported in the last 5 years (between 2015 and 2019). K E Y W O R D S alkaline phosphatase, inhibitors, isoenzymes, structure-activity relationship
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