BPIC: A novel anti-tumor lead capable of inhibiting inflammation and scavenging free radicals

Shan Li; Yuji Wang; Ming Zhao; Jianhui Wu; Shiqi Peng

doi:10.1016/j.bmcl.2014.12.013

BPIC: A novel anti-tumor lead capable of inhibiting inflammation and scavenging free radicals

Bioorg Med Chem Lett. 2015 Mar 1;25(5):1146-50. doi: 10.1016/j.bmcl.2014.12.013. Epub 2014 Dec 13.

Authors

Shan Li¹, Yuji Wang¹, Ming Zhao², Jianhui Wu¹, Shiqi Peng³

Affiliations

¹ Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China.
² Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China; Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: mingzhao@bjmu.edu.cn.
³ Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China. Electronic address: sqpeng@bjmu.edu.cn.

PMID: 25648297
DOI: 10.1016/j.bmcl.2014.12.013

Abstract

Inflammation has a critical role in the tumor progression, free radical damage can worse the status of patients in cancer condition. The anti-cancer agents capable of inhibiting inflammation and scavenging free radicals attract a lot of our interest. Aimed at the discovery of such anti-tumor agent, a novel intercalator, benzyl 1-[4-hydroxy-3-(methoxycarbonyl)-phenyl-9H-pyrido[3,4-b]indole-3-carboxylate (BPIC) was presented. The docking investigation of BPIC and doxorubicin towards the DNA (PDB ID: 1NAB) gave equal score and similar feature. The anti-proliferation assay of 8 cancer cells identified S180 cells had equal sensitivity to BPIC and doxorubicin. The anti-tumor assay defined the efficacy of BPIC been 2 folds higher than that of doxorubicin. At 1μmol/kg of dose BPIC effectively inhibited xylene-induced ear edema and decreased the plasma TNF-α and IL-8 of the mice. BPIC scavenged ∙OH, ∙O2(-) and NO free radicals in a concentration dependent manner and NO free radicals had the highest sensitivity. BPIC could be a novel anti-tumor lead capable of simultaneously inhibiting inflammation and scavenging free radicals.

Keywords: Anti-inflammation; Anti-tumor activity; Docking; Free radical; Lead.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacology*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Carbolines / chemistry
Carbolines / pharmacology*
Cell Line, Tumor
Free Radical Scavengers / chemistry
Free Radical Scavengers / pharmacology*
Free Radicals / immunology
Humans
Inflammation / drug therapy*
Inflammation / immunology
Intercalating Agents / chemistry
Intercalating Agents / pharmacology*
Mice
Molecular Docking Simulation
Neoplasms / drug therapy*
Neoplasms / immunology
Salicylates / chemistry
Salicylates / pharmacology*

Substances

Anti-Inflammatory Agents
Antineoplastic Agents
Carbolines
Free Radical Scavengers
Free Radicals
Intercalating Agents
Salicylates
benzyl 1-(4-hydroxy-3-(methoxycarbonyl)phenyl-9H-pyrido(3,4-b)indole-3-carboxylate