Schiff bases are synthetically accessible and structurally diverse compounds, typically obtained by facile condensation between an aldehyde, or a ketone with primary amines. Schiff bases contain an azomethine (-C = N-) linkage that stitches together two or more biologically active aromatic/heterocyclic scaffolds to form various molecular hybrids with interesting biological properties. Schiff bases are versatile metal complexing agents and have been known to coordinate all metals to form stable metal complexes with vast therapeutic applications. Areas covered: This review aims to provide a comprehensive overview of the various patented therapeutic applications of Schiff bases and their metal complexes from 2010 to 2015. Expert opinion: Schiff bases are a popular class of compounds with interesting biological properties. Schiff bases are also versatile metal complexing ligands and have been used to coordinate almost all d-block metals as well as lanthanides. Therapeutically, Schiff bases and their metal complexes have been reported to exhibit a wide range of biological activities such as antibacterial including antimycobacterial, antifungal, antiviral, antimalarial, antiinflammatory, antioxidant, pesticidal, cytotoxic, enzyme inhibitory, and anticancer including DNA damage.
Quinazoline and quinazolinone scaffolds represent an important class of biologically active nitrogen heterocyclic compounds. A variety of marketed drugs are based on these moieties. A diverse range of molecules with quinazoline/quinazolinone moieties have been reported to exhibit broad spectrum of biological activities. Area covered: This review covers recent efforts in the synthesis and biological screening of quinazoline/quinazolinone based compounds from 2011-2016. Expert opinion: Quinazoline and quinazolinones represent a diverse class of biologically active nitrogen heterocyclic compounds with immense therapeutic potential. Their ease of synthetic accessibility, and flexibility in structural modifications and functionalization further adds to their appeal in medicinal chemistry. A number of currently available drugs are based on quinazoline/quinazolinone scaffold. It is interesting to note that, among the recent patents available, a lot of them focus on the promising anticancer activity of quinazoline and quinazolinone containing compounds. However their biological activity is certainly not limited to anticancer only, they are also known to elicit a number of other biological and physiological effects in vitro and in vivo respectively. The interest in quinazolines and quinazolinones is ever growing, since they offer a fairly diverse chemical space for exploration of medicinal potential.
The modulatory role of extracellular nucleotides and adenosine in relevance to purinergic cell signaling mechanisms has long been known and is an object of much research worldwide. These extracellular nucleotides are released by a variety of cell types either innately or as a response to patho-physiological stress or injury. A variety of surface-located ecto-nucleotidases (of four major types; nucleoside triphosphate diphosphohydrolases or NTPDases, nucleotide pyrophosphatase/phosphodiesterases or NPPs, alkaline phosphatases APs or ALPs, and ecto-5'-nucleotidase or e5NT) are responsible for meticulously controlling the availability of these important signaling molecules (at their respective receptors) in extracellular environment and are therefore crucial for maintaining the integrity of normal cell functioning. Overexpression of many of these ubiquitous ecto-enzymes has been implicated in a variety of disorders including cell adhesion, activation, proliferation, apoptosis, and degenerative neurological and immunological responses. Selective inhibition of these ecto-enzymes is an area that is currently being explored with great interest and hopes remain high that development of selective ecto-nucleotidase inhibitors will prove to have many beneficial therapeutic implications. The aim of this review is to emphasize and focus on recent developments made in the field of inhibitors of ecto-nucleotidases and to highlight their structure activity relationships wherever possible. Most recent and significant advances in field of NTPDase, NPP, AP, and e5NT inhibitors is being discussed in detail in anticipation of providing prolific leads and relevant background for research groups interested in synthesis of selective ecto-nucleotidase inhibitors.
Alkaline phosphatase (AP, EC 3.1.3.1.) is a metalloenzyme that belongs to a family of ectonucleotidases. The other members of ectonucleotidase family are ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases), ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPPs) and ecto-5'-nucleotidase (e5'NT). These ectonucleotidases are responsible for hydrolyzing extracellular nucleotides to nucleosides including adenosine. Many of these extracellular nucleotides and adenosine are important signaling molecules that act on their respective receptors (adenosine activated P1 receptor; nucleotide activated P2 receptor, each having many sub-types) and are therefore responsible for triggering cellular responses that lead to important physiological and immunological changes. A dedicated, concerted cohort of ectonucleotidases is responsible for controlling the availability of these extracellular signaling molecules at their respective receptors. Inhibitors of these ectonucleotidases provide the means by which these cellular processes can be modulated. This mini review has been written in the wake of mounting evidence of potential therapeutic benefits associated with inhibition of alkaline phosphatases and aims to provide prolific leads to design more potent and selective AP inhibitors.
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