Abstract
Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators. Over the last twenty years, a large number of oximes have been reported with useful pharmaceutical properties, including compounds with antibacterial, anticancer, anti-arthritis, and anti-stroke activities. Many oximes are kinase inhibitors and have been shown to inhibit over 40 different kinases, including AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K), cyclin-dependent kinase (CDK), serine/threonine kinases glycogen synthase kinase 3 α/β (GSK-3α/β), Aurora A, B-Raf, Chk1, death-associated protein-kinase-related 2 (DRAK2), phosphorylase kinase (PhK), serum and glucocorticoid-regulated kinase (SGK), Janus tyrosine kinase (JAK), and multiple receptor and non-receptor tyrosine kinases. Some oximes are inhibitors of lipoxygenase 5, human neutrophil elastase, and proteinase 3. The oxime group contains two H-bond acceptors (nitrogen and oxygen atoms) and one H-bond donor (OH group), versus only one H-bond acceptor present in carbonyl groups. This feature, together with the high polarity of oxime groups, may lead to a significantly different mode of interaction with receptor binding sites compared to corresponding carbonyl compounds, despite small changes in the total size and shape of the compound. In addition, oximes can generate nitric oxide. This review is focused on oximes as kinase inhibitors with anticancer and anti-inflammatory activities. Oximes with non-kinase targets or mechanisms of anti-inflammatory activity are also discussed.
Highlights
Oximes have been studied for decades because of their significant roles as acetylcholinesterase reactivators
Oximes can inhibit FMS-like tyrosine kinase-3 (FLT3), which is recognized as a drug target for the treatment of acute myeloid leukemia (AML), as activating mutations of FLT3 have been found in ~30% of AML patients
Oxime groups have been successfully introduced into a large number of therapeutic leads for the development of kinase inhibitors with anticancer and anti-inflammatory activities
Summary
Oxime compounds have been investigated for decades because of their significant roles as acetylcholinesterase reactivators and their use as therapeutics for a number of diseases [1,2,3]. Oxime derivatives of gossypol, a of several natural compounds (Figure 1). Oxime derivatives of gossypol, a natural phenol derived from the cotton plant, exhibit antiviral, insecticidal, and fungicidal natural phenol derived from the cotton plant, exhibit antiviral, insecticidal, and fungicidal activity [31]. Another example is psammaplin A analog, the free oxime group which was activity [31]. Kinase and anticancer activity in comparison with the parent compound [33,34]. Acylated oximes derived from triterpenes have shown cytotoxic or liferative activity against many lines of cancer cells [35].
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