Synthesis and Cytotoxicity of N-Substituted Dibenzo[a,j]xanthene-3,11-dicarboxamide Derivatives.

Yongbin Song,Bo Liu,Hongrui Ji,Shang Gao,Yihui Yang,Lijun Wu,Guoyou Chen,Naiwei Dong,Xia Du

doi:10.3390/molecules22040517

Abstract

In order to study the structure-activity relationships of xanthene derivatives, four series of N-substituted 14-aryl-14H-dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by 1H-NMR, HR-MS and IR spectra, in which compounds 6a–h were further identified by 13C-NMR spectra. The in vitro antitumor activity of the synthesized compounds was tested by MTT assay. Most of them displayed strong inhibitory activity on human hepatocellular carcinoma cell lines (SK-HEP-1, HepG2 and SMMC-7721 cells) and acute promyelocytic leukemia NB4 cells. Compounds 6c–6e exhibited significant inhibitory activity against NB4 cells with IC50 values of 0.52 μM and 0.76 μM, respectively, much lower than 5.31 μM of the positive control As2O3.

Highlights

The benzoxanthenes have attracted considerable interest due to their biological and pharmacological activities such as antiviral [1], antibacterial [2], anti-inflammation [3], antitumor [4]and other usages in photodynamic therapy [5], and the antagonizing paralysis induced by zoxazolamine [6].In view of the great importance of benzoxanthenes, the preparation of which has been a hot research topic, there have been many research reports in recent years [7,8,9,10,11]
Compounds 4a–h were firstly converted into the corresponding acyl chlorides, and the intermediates were converted into corresponding dicarboxamides 5a–h with excessive gaseous NH3 ; they are easy to purify because they have little solubility in CHCl3 which was used as the solvent, and the reactants are soluble
All compounds were screened for their cytotoxicity against HepG2, SK-HEP-1, SMMC-7721 and NB4 cell lines

Summary

Introduction

The benzoxanthenes have attracted considerable interest due to their biological and pharmacological activities such as antiviral [1], antibacterial [2], anti-inflammation [3], antitumor [4]and other usages in photodynamic therapy [5], and the antagonizing paralysis induced by zoxazolamine [6].In view of the great importance of benzoxanthenes, the preparation of which has been a hot research topic, there have been many research reports in recent years [7,8,9,10,11]. The benzoxanthenes have attracted considerable interest due to their biological and pharmacological activities such as antiviral [1], antibacterial [2], anti-inflammation [3], antitumor [4]. We synthesized two series of dibenzo[a,j]xanthene-3,11-substituted compounds bearing a 2-hydroxyethyl group on the nitrogen atom (1a–i and 2a–c, Figure 1) [12]. The results of in vitro antitumor activity experiments revealed that compounds 1a–i and 2a–c exhibit remarkable inhibitory activity toward a wide range of human tumor cell lines. The amide derivatives 1a–c exhibit a stronger inhibitory effect than the amine derivatives 2a–c on tumor cell lines, implying that the amide group of dibenzo[a,j]xanthene derivatives is more critical than the amine group for improving the inhibitory activity toward tumor cells

Methods

Discussion

Conclusion