BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid

Abstract

Background:

In the discovery of DNA intercalators, β-carbolines compose one member of the most interesting alkaloid family and are of clinical importance. In the efforts, N-(3-benzyloxycarbonyl-β-carboline-1-yl)ethyl-Ser-Ala-OBzl (BCESA) was designed as a nano-scaled DNA intercalator without Dox-like toxicity.

Methods:

Based on the structural analysis and CDOCKER energy comparison, BCESA was rationally designed as such a nano-scaled intercalator. The anti-tumor activity, the toxicity and the tumor targeting action of BCESA were evaluated on mouse models.

Results:

The in vitro proliferation of cancer cells, but not non-cancer cells, was effectively inhibited by BCESA. On S180 mouse model BCESA dose-dependently slowed the tumor growth, and 0.01 μmol/kg/day was found as a minimal effective dose. Both BCESA and its moiety were found in the tumor tissue, but not in the organs and the blood, of S180 mice.

Conclusion:

BCESA should be a nano-scaled intercalator capable of targeting tumor tissue to release anti-tumoral β-carboline-3-carboxylic acid and its 1-methyl derivative, while Ser-Ala-OBzl is a simple and desirable carrier.

Keywords:

• nano-medicine
• β-carboline
• intercalator
• d(AGACGTCT)₂
• anti-tumor

Acknowledgments

The authors thank the Special Project of China (2018ZX097201003), NSFC (81703332, 81673303), BNSF (7172028), KZ201610025029, KM201810025010, KM201810025011 for financial support.

Disclosure

The authors report no conflicts of interest in this work