Asymmetric Synthesis and Cytotoxicity Evaluation of Right-Half Models of Antitumor Renieramycin Marine Natural Products

Takehiro Matsubara; Masashi Yokoya; Natchanun Sirimangkalakitti; Naoki Saito

doi:10.3390/md17010003

Asymmetric Synthesis and Cytotoxicity Evaluation of Right-Half Models of Antitumor Renieramycin Marine Natural Products

Mar Drugs. 2018 Dec 20;17(1):3. doi: 10.3390/md17010003.

Authors

Takehiro Matsubara¹, Masashi Yokoya², Natchanun Sirimangkalakitti³, Naoki Saito⁴

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. m176239@std.my-pharm.ac.jp.
² Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. yokoya@my-pharm.ac.jp.
³ Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. kikns@hotmail.com.
⁴ Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. naoki@my-pharm.ac.jp.

Abstract

A general protocol for the asymmetric synthesis of 3-N-arylmethylated right-half model compounds of renieramycins was developed, which enabled structure⁻activity relationship (SAR) study of several 3-N-arylmethyl derivatives. The most active compound (6a) showed significant cytotoxic activity against human prostate cancer DU145 and colorectal cancer HCT116 cell lines (IC₅₀ = 11.9, and 12.5 nM, respectively).

Keywords: 1,2,3,4-tetrahydroisoquinoline; asymmetric synthesis; cytotoxicity; marine natural product; renieramycin.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Biological Products / chemical synthesis*
Biological Products / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Screening Assays, Antitumor
Humans
Inhibitory Concentration 50
Molecular Structure
Porifera / chemistry*
Structure-Activity Relationship
Tetrahydroisoquinolines / chemical synthesis
Tetrahydroisoquinolines / pharmacology*

Substances

Antineoplastic Agents
Biological Products
Tetrahydroisoquinolines