Design, synthesis, and cytotoxic activity of 2-amino-1,4-naphthoquinone-benzamide derivatives as apoptosis inducers

Abstract

Abstract A new series of 2-amino-1,4-naphthoquinone-benzamides 5a-n was designed based on previously reported potent cytotoxic agents. These compounds were synthesized from the reaction of 1,4-naphthoquinone, 4-aminobenzoic acid, and appropriate amine derivatives in good yields. Cytotoxic activities of the target compounds 5a-n were evaluated against three cancer cell lines MDA-MB-231, SUIT-2, and HT-29 by MTT assay and the obtained in vitro data. All newly synthesized compounds were more potent than positive control cisplatin against MDA-MB-231 cell line and less potent than this control against SUIT-2 cell line. Moreover, most of the synthesized compounds were more potent than cisplatin against HT-29 cell line. Among the synthesized compounds, compound 5e was the most potent cytotoxic agent against all the three evaluated cell lines. Moreover, cell cycle analysis showed that derivatives 5f and 5l dose-dependently increase the percentage of sub-G1 cells. Induction of apoptosis as an important mechanism of anti-cancer drugs was confirmed morphologically in the most potent new compounds 5e, 5f, 5g, and 5l by Hoechst 33,258 staining.

Keywords

• 2-Amino-1,4-naphthoquinon
• Benzamide
• Apoptosis
• Cytotoxic