To date, a large number of MMP inhibitors based on hydroxamic acid derivatives or other synthetic inhibitors have been designed.
Desferal, deferiprone and deferasirox, chelating agents nowadays in use, are based on hydroxamic groups, hydroxyl-substituted pyridinones or aromatic ring systems.
In the present study, a series of 1,3,4-thiadiazole based hydroxamic acids were developed as potent HDAC inhibitors.
HDACIs are specific for class I and II or class III HDACs and have been subdivided into four distinct groups based on their structural characteristics: hydroxamic acids; short-chain fatty acids; synthetic benzamide derivatives; cyclic tetrapeptides/epoxides [39], [46], [47].
Among the HDAC inhibitors, which can be categorized based on their structure, suberoylanilide hydroxamic acid (SAHA) was first approved for therapy for cutaneous T-cell lymphoma in 2006 [ 10].
We report here the design and parallel synthesis of 217 compounds based on a malonic hydroxamic acid template.
Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors.
By combining the structural features of known inhibitors of inosine monophosphate dehydrogense (IMPDH) and histone deacetylase (HDAC), dual inhibitors of IMPDH and HDAC based on the scaffold of cinnamic hydroxamic acid (CHA) have been designed, synthesized, and evaluated in biological assays.
HDACis can be divided into four classes based on different chemical properties: short-chain fatty acids, hydroxamic acids, cyclic peptides, and benzamides (Table 1).
Compared with tetrahydroisoquinoline-based hydroxamic acids, tyrosine-based hydroxamic acid derivatives exhibited more potent HDAC8 inhibitory activity.
