Comparative analysis of p-terphenylquinone and seriniquinone derivatives as reactive oxygen species-modulating agents

Haruna Nagao; Masayuki Ninomiya; Hodaka Sugiyama; Atsuya Itabashi; Kaho Uno; Kaori Tanaka; Mamoru Koketsu

doi:10.1016/j.bmcl.2022.128992

Comparative analysis of p-terphenylquinone and seriniquinone derivatives as reactive oxygen species-modulating agents

Bioorg Med Chem Lett. 2022 Nov 15:76:128992. doi: 10.1016/j.bmcl.2022.128992. Epub 2022 Sep 17.

Authors

Haruna Nagao¹, Masayuki Ninomiya², Hodaka Sugiyama¹, Atsuya Itabashi¹, Kaho Uno¹, Kaori Tanaka³, Mamoru Koketsu⁴

Affiliations

¹ Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
² Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Division of Instrumental Analysis, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
³ Division of Anaerobe Research, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan; United Graduate School of Drug Discovery and Medicinal Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan; Division of Cooperative Research Facility, Institute for Glyco-core Research (iGCORE), Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
⁴ Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. Electronic address: koketsu@gifu-u.ac.jp.

PMID: 36126897
DOI: 10.1016/j.bmcl.2022.128992

Abstract

Quinones are widespread in plants, animals, insects, and microorganisms. Several anticancer agents contain quinone structures as critical parts to show remarkable potential and distinctive modes of actions. The purpose of this study was to investigate the structure-activity relationships of microbial quinones and their derivatives as anticancer agents. A series of p-terphenylquinone and seriniquinone derivatives were therefore prepared. Treatment of the synthesized quinones possessed antiproliferative activity on human leukemia HL-60 cells in a dose-dependent fashion. In addition, seriniquinone derivatives elevated cellular reactive oxygen species (ROS) levels, thereby triggering the ensuing apoptotic events. Our findings emphasize the excellent potential of seriniquinone derivatives as redox cycling-induced ROS-modulating anticancer agents.

Keywords: Apoptosis; Microbial quinone; P-Terphenylquinone; Reactive oxygen species; Seriniquinone.

MeSH terms

Animals
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
HL-60 Cells
Humans
Oxidation-Reduction
Quinones* / chemistry
Quinones* / pharmacology
Reactive Oxygen Species

Substances

Antineoplastic Agents
p-terphenylquinone
Quinones
Reactive Oxygen Species
seriniquinone