Design and synthesis of novel hydroxyanthraquinone nitrogen mustard derivatives as potential anticancer agents via a bioisostere approach

Abstract

A series of hydroxyanthraquinones having an alkylating N-mustard pharmacophore at 1′-position were synthesized via a bioisostere approach to evaluate their cytotoxicity against four tumor cell lines (MDA-MB-231, HeLa, MCF-7 and A549). These compounds displayed significant in vitro cytotoxicity against MDA-MB-231 and MCF-7 cells, reflecting the excellent selectivity for the human breast cancer. Among them, compound 5k was the most cytotoxic with IC50 value of 0.263 nM and is more potent than DXR (IC50 = 0.294 nM) in inhibiting the growth of MCF-7 cells. The excellent cytotoxicity and good selectivity of compound 5k suggest that it could be a promising lead for further design and development of anticancer agents, especially for breast cancer.

Preparation of Conjugated Polymer Grafted with H2O2-Sensitive Prodrug for Cell Imaging and Tumor Cell Killing

“…Whereas, compound 4 had no obvious cytotoxicity toward the two types of tumor cells (Figure S3), suggesting that the cell killing ability of compound 2 and PFP-Chl resulted from chlormethine release triggered by the overproduced H 2 O 2 in tumor cells. The experimental results are consistent with the reported research that HeLa cells are more sensitive to nitrogen mustard than A549 cells do …”

“…The experimental results are consistent with the reported research that HeLa cells are more sensitive to nitrogen mustard than A549 cells do. 30 In conclusion, we synthesized a new H 2 O 2 -sensitive prodrug (compound 2) with an eight-member-cyclic boronate ester, which would suffer from H 2 O 2 -triggered nitrogen mustard release and further DNA cross-linking and alkylation. The…”

One-pot synthesis of 1,4-dihydroxy-2-(( E )-1-hydroxy-4-phenylbut-3-enyl)anthracene-9,10-diones as novel shikonin analogs and evaluation of their antiproliferative activities

“…Based on the biological significance of quinizarin and cinnamyl moieties an ongoing research program in our laboratory has focused on developing bioactive anthraquinones. 25–29 We envisioned that the combination of these moieties into one molecule to mimic the structure of shikonin might create a new class of natural product-like molecules with improved therapeutic index compared to shikonin. The resulting molecules may confer desirable biological activities.…”