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

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.

Synthesis of fluorescent drug molecules for competitive binding assay based on molecularly imprinted polymers.

Fluorescent immunosorbent assay (FIA) is very promising for sensitive and selective analysis in bio-medical applications. Here, we proposed an assay, using fluorescent engineering of analytes and the corresponding molecularly imprinted polymers (MIPs) as a plastic antibody. Three drug molecules (metronidazole, zidovudine and lamivudine) were condensed with 9-aminoacridine, using succinic anhydride as a spacer. The target products were characterized with 1H-NMR, IR and mass spectrometry. UV-vis absorption and fluorescent properties of the fluorophore-labeled drug molecules were investigated. Feasibility of the fluorescent biomimetic immunosorbent assay based on MIPs was demonstrated in the solution. This work will provide sound foundation for the future application in real sample.

[Inhibitory activity of dioxy-pyrrolino [3', 4'-d]isoxazoline derivatives containing (1', 2'-O-cyclohexylidendioxyethyl) against Cdc25A and CD45].

Fifteen 3-(1', 2'-di-O-cyclohexylidendioxyethyl)-5-aryl-3a, 6a-dihydro-4, 6-dioxo-pyrrolino[3', 4'-d] isoxazoline derivatives (3a-3o) were synthesized by 1, 3-dipolar cycloaddition reaction of N-arylmaleimides and the nitrile oxide in situ generated from 2, 3-O-cyclohexylidene-D-glycerohydroximoyl chloride, in the presence of triethylamine. The structures of the target compounds 3a-3o were characterized by 1H NMR, IR and elemental analysis. The preliminary bioassay on the compounds showed that some compounds possess in vitro anticancer activity and the leukocyte common antigen activity to a different extent. The compounds 3e, 3h, 3j and 31 showed Cdc25A phosphatase inhibitory activity of 60.6%, 58.6%, 51.4% and 98.4% respectively at the test concentration of 20 microg x mL(-1), and among them 31 had inhibition rate of 86.97% even at the concentration as low as 5 microg x mL(-1), indicating worthy to be future studied. The compounds 3e, 31 and 3n showed an inhibitory activity of 57.7%, 74.4% and 77.3% on CD45 protein tyrosine phosphatase A, respectively, at the test concentration of 20 micromol x mL(-1). The structure-activity relationship of 3-(1', 2'-di-O-cyclohexylidendioxyethyl)-5-aryl-3a, 6a- dihydro-4, 6-dioxo-pyrrolino[3', 4'-d]isoxazoline derivatives was also discussed.