Next Article in Journal
In Vitro Acylation of Okadaic Acid in the Presence of Various Bivalves’ Extracts
Previous Article in Journal
Isolation and Purification of a Peptide from Bullacta exarata and Its Impaction of Apoptosis on Prostate Cancer Cell
Mar. Drugs 2013, 11(2), 274-299; doi:10.3390/md11020274
Article

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

 and
*
Received: 4 December 2012 / Revised: 16 January 2013 / Accepted: 21 January 2013 / Published: 28 January 2013
View Full-Text   |   Download PDF [1112 KB, uploaded 24 February 2015]   |   Browse Figures

Abstract

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 (Kapp 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.
Keywords: marine natural products; styelsamine; cystodytin; pyridoacridine; DNA binding marine natural products; styelsamine; cystodytin; pyridoacridine; DNA binding
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplements

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote
MDPI and ACS Style

Fong, H.K.H.; Copp, B.R. Synthesis, DNA Binding and Antitumor Evaluation of Styelsamine and Cystodytin Analogues. Mar. Drugs 2013, 11, 274-299.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert