Acridone Alkaloids from Glycosmis chlorosperma as DYRK1A Inhibitors

Abstract

Two new acridone alkaloids, chlorospermines A and B (1 and 2), were isolated from the stem bark of Glycosmis chlorosperma, together with the known atalaphyllidine (3) and acrifoline (4), by means of bioguided isolation using an in vitro enzyme assay against DYRK1A. Acrifoline (4) and to a lesser extent chlorospermine B (2) and atalaphyllidine (3) showed significant inhibiting activity on DYRK1A with IC50's of 0.075, 5.7, and 2.2 μM, respectively. Their selectivity profile was evaluated against a panel of various kinases, and molecular docking calculations provided structural details for the interaction between these compounds and DYRK1A.

Recent developments in the synthesis and biological activity of acridine/acridone analogues

“…47 Mohammadi-Khanaposhtani et al presented the synthesis of triazole derivatives of acridone (44a-n) (Scheme 2). 49 In the rst step, 2-arylamino benzoic acids (39) were obtained by the Ullmann condensation reaction of 2-bromobenzoic acid (37) and various aniline derivatives (38) in the presence of potassium carbonate and copper in EtOH at reux. Subsequent cyclization of compound (39) by PPA at 100 C obtained acridone derivatives (40), which by reaction with propargyl bromide (41) using potassium tert-butoxide in DMSO at room temperature yielded 10-(prop-2-yn-1-yl)acridin-9-one derivatives (42).…”

“…50 Mohammadi-Khanaposhtani et al presented the synthesis of novel acridone-based 1,2,4-oxadiazoles (57a-n) as potential anticonvulsant agents. In the rst step, 2-arylamino benzoic acids (49) were prepared by the Ullmann condensation reaction of 2-bromobenzoic acid (37) and different anilines (48). 51 Then, the cyclization of compounds (49) by PPA yielded acridone derivatives (50).…”

Synthesis of 3‐Methylidene‐1‐tosyl‐2,3‐dihydroquinolin‐4(1H)‐ones as Potent Cytotoxic Agents

“…In recent years, compounds containing 2,3‐dihydroquinolin‐4‐one skeleton have attracted considerable interest, mainly due to their interesting biological activities. This system can be found in many natural products [ ][ ] and is responsible for pharmacological properties of a large number of drugs or drug candidates . An important, but poorly recognized group of synthetic 2,3‐dihydroquinolin‐4(1 H )‐ones are their 3‐alkylidene(arylidene) derivatives 1 which contain an exo ‐alkylidene(arylidene) bond conjugated with a carbonyl group ( Figure ).…”

Tandem Access to Acridones and their Fused Derivatives: [1+2+3] Annulation of Isocyanides with Unsaturated Carbonyls

“…Acridones and their fused frameworks are prominent moieties in many natural products, anticancer drugs, anti‐malarials and biomaterials . Moreover, the acridones are also served as useful building blocks for the construction of organic semiconductors, dyestuffs and fluorescent labels .…”