Design, synthesis, and testing of an isoquinoline-3-carboxylic-based novel anti-tumor lead

Fei Gao; Haiqing Liu; Li Li; Jianpeng Guo; Yuji Wang; Ming Zhao; Shiqi Peng

doi:10.1016/j.bmcl.2015.09.014

Design, synthesis, and testing of an isoquinoline-3-carboxylic-based novel anti-tumor lead

Bioorg Med Chem Lett. 2015 Oct 15;25(20):4434-6. doi: 10.1016/j.bmcl.2015.09.014. Epub 2015 Sep 7.

Authors

Fei Gao¹, Haiqing Liu¹, Li Li², Jianpeng Guo¹, Yuji Wang¹, Ming Zhao³, Shiqi Peng¹

Affiliations

¹ Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center 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 Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China. Electronic address: [email protected].
³ Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center 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: [email protected].

PMID: 26386603
DOI: 10.1016/j.bmcl.2015.09.014

Abstract

Compound 6, a novel isoquinoline comprising two isoquinoline-3-carboxylic acids and a benzoic acid conjugated together using tris(2-aminoethyl)amine, was synthesized and tested for anti-tumor activity. In vivo evaluations found 6 to be well tolerated, of high therapeutic efficacy and of low systemic toxicity, at effective doses. The results suggest 6 to be a promising lead for future study, and the use of multiple isoquinoline-3-carboxylic acid moieties as pharmacophores in the same molecule to be a useful strategy for the design of anti-tumor drugs.

Keywords: Anti-tumor; Benzoic acid; Isoquinoline-3-carboxylic acid; Multiple pharmacophores; Tris(2-aminoethyl)amine.

Publication types

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

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Benzoates / chemical synthesis
Benzoates / chemistry
Benzoates / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
Humans
Isoquinolines / chemical synthesis
Isoquinolines / chemistry
Isoquinolines / pharmacology*
Mice
Molecular Structure
Neoplasms, Experimental / drug therapy
Neoplasms, Experimental / pathology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzoates
Isoquinolines
isoquinoline-3-carboxylic acid