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Based on the molecular modelling studies, a rational modification of the lead molecule was made to develop highly potent compounds showing anti-cancer activity against human breast cancer cell lines MCF 7, MDA-MB-468 and T-47D. The most potent compounds have Log P and total polar surface area 4.4–5.4 and 59.8 A, respectively and they also exhibited promising ADME profile.

Targeting dihydrofolate reductase, here, we report the tumor growth inhibitory activity of substituted acridones. The screening of the molecules over 60 cell line panel of human cancer cells identified (S)-oxiran-2-ylmethyl 9-oxo-9,10-dihydroacridine-4-carboxylate (19) with average GI50 0.3 μM. The specificity of the compound to CCRF-CEM, MOLT-4 and SR cell lines of leukemia and SW-620, SF268, LOXIMVI, ACHN and MCF7 cancerous cells exhibiting GI50 in the nM range was observed. C6 Glioma cells treated with compound 19 showed differentiated cell morphology and cell cycle arrest in G2/M phase. The interactions of the compound with dihydrofolate reductase were ascertained with the help of enzyme immunoassays, molecular docking and molecular dynamic studies.

On the basis of the chemical structures of psorospermin with a xanthone template and acronycine derivatives with an acridone template, rac-1 and rac-2 constructed on an 1,2-dihydrobenzofuro[4,5-b][1,8]naphthyridin-6(11H)-one scaffold were designed and synthesized as potential anticancer agents. Their anticancer activities were evaluated against five human cancer cell lines. Rac-2 showed similar anticancer activity to doxorubicin and rac-1 exhibited even higher anticancer activity against LNCaP (IC(50)=0.14 μM), DU145 (IC(50)=0.15 μM), PC3 (IC(50)=0.30 μM) and MCF-7 (IC(50)=0.26 μM) cancer lines than doxorubicin and rac-2. Also, rac-1 revealed very potent anticancer activity (IC(50)=0.15 μM) against MCF-7/ADR cell (doxorubicin-resistant breast cancer cell) lines and induced G2/M phase arrest of the cell cycle in MCF-7/ADR cells.

Heme is an important prosthetic molecule for various hemoproteins and serves important function in living aerobic organisms. But degradation of hemoprotein, for example, hemoglobin during different pathological conditions leads to the release of heme, which is very toxic as it induces oxidative stress and inflammation due to its pro-oxidant nature. Thus, synthesis of compound that will detoxify free heme by interacting with it would be fruitful for the management of heme-induced pathogenesis. Here, we report the synthesis of a novel natural product arborinine and some other acridone derivatives, which interact with free heme. These acridones in vitro block heme-mediated protein oxidation and degradation, markers for heme-induced oxidative stress.

A series of 4,5-di-substituted acridones have been designed and synthesized. Several compounds show high affinity for telomeric G-quadruplex DNA in classical and competition FRET assays, together with low duplex DNA affinity, although they do not show activity in a telomerase assay or evidence of telomere shortening. They have low toxicity against a panel of cancer cell lines and a normal human fibroblast line, and produce potent senescence-based long-term growth arrest in the MCF7 and A549 cancer cell lines.

Triphosphate of a thymidine analogue bearing acridone was prepared and incorporated as a substrate for PCR using KOD Dash DNA polymerase forming a new fluorescent-labeled DNA that is useful as a DNA probe.

A series of 5-hydroxy-4-quinolone ( 3 ) and 5-methoxy-4-quinolone ( 4 ) derivatives were synthesized as truncated acridone analogues and evaluated for antitumor and antiherpes activities. Among them 5-hydroxy-8-methoxy-quinolone showed potent antitumor activity (IC 50 = 17.7 μM for HL60) which was greater than that of acronycine.