(-)-Shikimic Acid as a Chiral Building Block for the Synthesis of New Cytotoxic 6-Aza-Analogues of Angucyclinones

Abstract

We describe the syntheses of nine new angucyclinone 6-aza-analogues, achieved through a hetero Diels-Alder reaction between the shikimic acid derivative-azadiene 13, with different naphthoquinones. The cytotoxic activity of the new synthesized compounds and five angucyclinones, previously reported, was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and one non-tumoral cell line, human colon epithelial cells (CCD841 CoN). Our results showed that most 6-azadiene derivatives exhibited significant cytotoxic activities, which was demonstrated by their IC50 values (less than 10 μM), especially for the most sensitive cells, PC-3 and HT-29. From a chemical point of view, depending on the protected group of ring A and the pattern of substitution on ring D, cytotoxicity elicited these compounds, in terms of their potency and selectivity. Therefore, according to these chemical features, the most promising agents for every cancer cell line were 7a, 17, and 19c for PC-3 cells; 7a, 17, and 20 for HT-29 cells, and 19a for MCF-7 cells.

Cytotoxic Activity, Topoisomerase I Inhibition and In Silico Studies of New Sesquiterpene-aryl Ester Derivatives of (-) Drimenol

“…To establish whether synthesized sesquiterpene derivatives possess potential antitumor properties, their cytotoxic effects were determined in vitro in a panel of human cancer cell lines [24] and their effects on a non-neoplastic cell line as a control. For this purpose, a colorimetric sulforhodamine B assay was performed to quantify the cytotoxic effect through their respective IC 50 values [25,26]. Each compound's serial dilutions (12.5, 25, 50, and 100 µM) were evaluated in triplicate.…”

Microwave‐Assisted Three‐Component Synthesis of Novel N‐Arylated‐Dihydrobenzo[g]quinoline‐5,10‐Diones and Their Potential Cytotoxic Activity

“…[15,16] The synthesis of this privileged structure has, therefore, attracted the significant interest of chemists. [17][18][19][20][21][22][23][24][25][26][27][28][29][30] The classical synthetic routes of several 1-aza-anthraquinones have usually involved a hetero-Diels-Alder reaction between an azadiene and naphthoquinone, [17,18] a cycloisomerization of Npropargylaminoquinone, [19][20][21] the Friedel-Crafts approach, [22] radical couplings using 2-amino-1,4naphthoquinones. [23][24][25] Recently, metal-free, one-pot reactions of 3-formylchromones and 2-aminonaphthalene-1,4-dione have been developed to afford 3-(2-hydroxybenzoyl)-1-aza-anthraquinone derivatives.…”

“… [12–14] Aza‐anthraquinones such as pixantrone ( Figure 1) have also known as anti‐cancer chemotherapeutic agents that interact with DNA through intercalation [15,16] . The synthesis of this privileged structure has, therefore, attracted the significant interest of chemists [17–30] . The classical synthetic routes of several 1‐aza‐anthraquinones have usually involved a hetero‐Diels‐Alder reaction between an azadiene and naphthoquinone, [17,18] a cycloisomerization of N ‐propargylaminoquinone, [19–21] the Friedel‐Crafts approach, [22] radical couplings using 2‐amino‐1,4‐naphthoquinones [23–25] .…”