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Current Organic Synthesis

Author(s): Hao Li, Buer Song, Mamtimin Mahmut* and Mukhtar Imerhasan*

DOI: 10.2174/1570179417666201228165500

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One-Pot Green Synthesis of Acridine Alkaloid Derivatives and Screening of in vitro Anti-cancer Activity Against Cdc25b and SHP1

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Abstract

Aim: To develop anti-cancer active pharmaceutical intermediates.

Background: Acridone derivatives possess a wide range of pharmacological activities: 1) they intercalate DNA and 2) form a covalent bond with DNA.

Objective: To screen in vitro anti-cancer activity against Cdc25b and SHP1 of new acridone derivatives and preliminary study on the structure-activity relationship.

Materials and Methods: The synthesis of new acridone derivatives and in vitro evaluation of their anti-cancer activity on Cdc25b and SHP1 was achieved. Natural products that contain acridine structures, such as cystodytin A and acronycine, are isolated from certain marine (tunicates & ascidians, sponges, sea anemones) and plant (bark of Australian scrub ash tree) species. Herein, we report the efficient one-pot green synthesis of twelve novel 3,4-dihydro-1 (2H) acridone derivatives, using montmorillonite K10 as the catalyst and iron/citric acid in water. Also, their inhibitory activity against Cdc25B and SHP1 is examined, in which specific derivatives show enhanced inhibitory activity compared to others.

Results and Discussion: Twelve new acridone derivatives were prepared, starting from 2-nitrobenzaldehyde derivatives and 1, 3-cyclohexanedione derivatives, which exhibited substantial anti-cancer activity against Cdc25b and SHP1 cells.

Conclusion: Preliminary studies on the structure-activity relationship have shown the influence of the structural parameters and, in particular, the nature of the substituent on aromatic ring structure and cyclohexanone.

Other: Further study on the structure-activity relationship is required.

Keywords: One-pot synthesis, in vitro anti-cancer activity, natural product analogs, acridone, alkaloid derivatives, Cdc25b, SHP1.

Graphical Abstract

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