Abstract
Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 ± 0.21 and 8.50 ± 1.18 μg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques.
Highlights
Anthraquinone compounds, especially anthracyclines, have long been used as effective anticancer drugs
The current study describes the total synthesis of damnacanthal (1) and nordamnacanthal (2) with modified reaction steps, their cytotoxic activities of against MCF-7 and K-562 cancer cell lines and their structure activity relationships (SARs)
Anthraquinone skeletons are generally synthesized by Friedel-Crafts acylation condensation between phthalic anhydride and benzene derivatives [29]. 1,3-Dihydroxy-2-methylanthraquinone (3) was used as the common precursor for the synthesis of damnacanthal (1) and nordamnacanthal (2)
Summary
Anthraquinone compounds, especially anthracyclines, have long been used as effective anticancer drugs. Depending on their chemical structure, anthraquinone drugs can kill tumor cells by diverse mechanisms, involving different initial intracellular targets that normally contribute to drug-induced toxicity [1,2,3]. The detail study on anthraquinones has revealed that a range of DNA-recognizing molecules that act as antitumor agents, including groove binders, alkylating and intercalator compounds. DNA intercalators have attracted particular attention because of their antitumor activity. A number of acridine and anthracycline compounds are excellent DNA intercalators that are on the market as chemotherapeutic agents [15,16]
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