Synthesis, DNA Binding and Antitumor Evaluation of Styelsamine and Cystodytin Analogues

Marine Drugs

Hugo K. H. Fong¹ 

[1] School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand; E-Mail

关键词: marine natural products;    styelsamine;    cystodytin;    pyridoacridine;    DNA binding;   

DOI  :  10.3390/md11020274

来源: mdpi

【 摘 要 】

A series of N-14 sidechain substituted analogues of styelsamine (pyrido[4,3,2-mn]acridine) and cystodytin (pyrido[4,3,2-mn]acridin-4-one) alkaloids have been prepared and evaluated for their DNA binding affinity and antiproliferative activity towards a panel of human tumor cell lines. Overall it was found that styelsamine analogues were stronger DNA binders, with the natural products styelsamines B and D having particularly high affinity (K_app 5.33 × 10⁶ and 3.64 × 10⁶ M⁻¹, respectively). In comparison, the cystodytin iminoquinone alkaloids showed lower affinity for DNA, but were typically just as active as styelsamine analogues at inhibiting proliferation of tumor cells in vitro. Sub-panel selectivity towards non-small cell lung, melanoma and renal cancer cell lines were observed for a number of the analogues. Correlation was observed between whole cell activity and clogP, with the most potent antiproliferative activity being observed for 3-phenylpropanamide analogues 37 and 41 (NCI panel average GI₅₀ 0.4 μM and 0.32 μM, respectively) with clogP ~4.0–4.5.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.