Synthesis and Antineoplastic Efficacy of Anthraquinone and Saturated Fatty Acid Conjugates

Abstract

AbstractThe clinical use of anthraquinone antibiotics such as doxorubicin in cancer chemotherapy is limited due to their toxic cardiomyopathy effects. The conjugation of anthraquinones with fatty acids is known to enhance bioactivity by increasing lipophilicity and facilitating cell membrane permeation. Short‐chain saturated fatty acids such as capric, caprylic, caproic acids, and lauric acids are known for their inherent anticancer properties on human colorectal cancer cells. In this study, 2‐hydroxyanthraquinone and saturated fatty acid esters were synthesized and evaluated against human colon cancer cell line HT‐29 and Colo‐205, breast cancer cell lines MDA‐MB‐231 and MCF‐7, and leukemia cell line K‐562 for their in vitro anticancer properties using a sulforhodamine B (SRB) assay. The anthraquinone‐saturated fatty acid conjugates produced excellent activity against human colon and breast cancer cell lines. The octanoic acid and hexanoic acid derivatives of 2‐hydroxy anthraquinone showed excellent anticancer activity with GI50 values of 0.2 nM and 1.0 nM against human colon cancer cell line Colo‐205 and the human breast cancer cell line MCF‐7, respectively, and emerged as the most active compounds. Furthermore, the in vitro cytotoxicity study against peripheral blood mononuclear cells showed that these derivatives are non‐toxic in nature.