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

Abstract

Aims: To develop of anticancer active pharmaceutical intermediates. Background: Acridone derivatives possesses wide range of pharmacological activities:1) intercalate DNA 2) form covalent bond with DNA. Objective: To Screening of in vitro anticancer activity against Cdc25b and SHP1 of new acridone derivatives and preliminary study on structure-activity relationship. Materials and Methods: Synthesis of new acridone derivatives and in vitro evaluation of their anticancer activity on Cdc25b and SHP1. 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: Starting from 2-nitrobenzaldehyde derivatives and 1, 3-cyclohexanedione derivatives, twelve new acridone derivatives were prepared and exhibited substantial anticancer activity against Cdc25b and SHP1 cells. Conclusion: Preliminary studies of 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 structure-activity relationship.

Iron-Catalyzed Annulation of 2-Aminobenzaldehydes with Iodonium Ylides: A Mild and General Route for the Synthesis of Acridinone Derivatives

“…3-Phenyl-3,4-dihydroacridin-1(2H)-one (3ac) [43]: Yield: 0.098 g, 92%, 1 H NMR (500 MHz, CDCl3, δ ppm): 8.89 (s, 1H), 8.11 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.83 (t, J = 7.5 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7. 39-7.32 (m, 4H), 7.29-7.26 (m, 1H), 3.68-3.58 (m, 2H), 3.54-3.49 (m, 1H), 3.13-3.12 (m, 1H), 3.01-2.96 (m, 1H).…”

Innovative and sustainable synthesis and structure of novel N‐substituted hexahydroacridine derivatives

“…12 Acridine molecule is also one of the most versatile and well-known heterocyclic nuclei, which is seen as common and integral feature of natural products, polymers and medicinal agents. 13,14 Moreover, acridine undergoes a number of organic reactions such as nucleophilic addition, electrophilic substitution, oxidation, reduction, reductive alkylation, and photo alkylation. 15 A multitude of acridines and substituted acridines as corrosion inhibitors of different metals and alloys in various corrosive media have been studied.…”

“… 11 In addition, acridine exists as a part in various therapeutic agents like quinacrine (antimalarial), ethacridine (abortifacient), amsacrine and nitracine (anticancer), and tacrine 12 . Acridine molecule is also one of the most versatile and well‐known heterocyclic nuclei, which is seen as common and integral feature of natural products, polymers and medicinal agents 13,14 . Moreover, acridine undergoes a number of organic reactions such as nucleophilic addition, electrophilic substitution, oxidation, reduction, reductive alkylation, and photo alkylation 15 …”