Structure-activity relationship study of 4,5-didehydroguadiscine, an aporphine alkaloid showing potent melanogenesis-inhibitory activity in B16 melanoma cells

Katsuki Takashima; Miyu Teramachi; Shinsuke Marumoto; Fumihiro Ishikawa; Yoshiaki Manse; Toshio Morikawa; Genzoh Tanabe

doi:10.1016/j.bmcl.2022.129034

Structure-activity relationship study of 4,5-didehydroguadiscine, an aporphine alkaloid showing potent melanogenesis-inhibitory activity in B16 melanoma cells

Bioorg Med Chem Lett. 2022 Dec 15:78:129034. doi: 10.1016/j.bmcl.2022.129034. Epub 2022 Oct 20.

Authors

Katsuki Takashima¹, Miyu Teramachi¹, Shinsuke Marumoto², Fumihiro Ishikawa¹, Yoshiaki Manse³, Toshio Morikawa⁴, Genzoh Tanabe⁵

Affiliations

¹ Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
² Joint Research Center, and Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
³ Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
⁴ Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. Electronic address: morikawa@kindai.ac.jp.
⁵ Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan; Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. Electronic address: g-tanabe@phar.kindai.ac.jp.

PMID: 36273707
DOI: 10.1016/j.bmcl.2022.129034

Abstract

Although 4,5-didehydroguadiscine (12a), an alkaloid with potent melanogenesis-inhibitory activity isolated from Hornschuchia obliqua (Annonaceae), consists of an aporphine nucleus with an aromatized B-ring, to date, it has not been utilized as a template for structure-activity relationship (SAR) studies of pharmacological activities because of its exceptional structure. Accordingly, herein, five analogs (12b-12f) of 12a and five benzylisoquinoline analogs (13b-13f) lacking the C11a-C11b bond of 12b-12f were prepared. The inhibitory effects of 12b-12f and 13b-13f on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were examined and compared with those of 12a. Melanogenesis-inhibitory activities of 12b-12f were the same as that of 12a, whereas the melanogenesis-inhibitory activities of 13b-13f were significantly inferior to those of 12a and 12b-12f. These results suggest that the C11a-C11b bond plays an essential role in the melanogenesis-inhibitory activities of 12a-12e.

Keywords: Alkaloid; Aporphine-type compound; Benzylisoquinoline-type compound; Melanogenesis inhibitor; SAR study.

Publication types

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

MeSH terms

Alkaloids* / chemistry
Animals
Antineoplastic Agents* / pharmacology
Aporphines* / pharmacology
Cell Line, Tumor
Melanins
Melanoma, Experimental* / drug therapy
Molecular Structure
Structure-Activity Relationship

Substances

4,5-didehydroguadiscine
Melanins
Aporphines
Alkaloids
Antineoplastic Agents