Melosuavine I, an apoptosis-inducing bisindole alkaloid from Melodinus suaveolens

Zhong-Ying Fang; Yi-Dan Ren; Si-Yu Du; Miao Zhang; Yun-Shan Wang; Lei Fang; Hua Zhang

doi:10.1016/j.fitote.2018.12.026

Melosuavine I, an apoptosis-inducing bisindole alkaloid from Melodinus suaveolens

Fitoterapia. 2019 Mar:133:175-179. doi: 10.1016/j.fitote.2018.12.026. Epub 2019 Jan 18.

Authors

Zhong-Ying Fang¹, Yi-Dan Ren², Si-Yu Du³, Miao Zhang⁴, Yun-Shan Wang², Lei Fang⁵, Hua Zhang⁶

Affiliations

¹ School of Biological Sciences and Technology, University of Jinan, Jinan 250022, PR China; Key laboratory of Natural Pharmaceutical Chemistry, Shandong University of Traditional Chinese Medicine, Jinan 250200, China.
² International Biotechnology R&D Center, School of Ocean, Shandong University, Weihai 264209, China.
³ Key laboratory of Natural Pharmaceutical Chemistry, Shandong University of Traditional Chinese Medicine, Jinan 250200, China.
⁴ School of Biological Sciences and Technology, University of Jinan, Jinan 250022, PR China.
⁵ School of Biological Sciences and Technology, University of Jinan, Jinan 250022, PR China; Key laboratory of Natural Pharmaceutical Chemistry, Shandong University of Traditional Chinese Medicine, Jinan 250200, China. Electronic address: bio_fangl@ujn.edu.cn.
⁶ School of Biological Sciences and Technology, University of Jinan, Jinan 250022, PR China. Electronic address: bio_zhangh@ujn.edu.cn.

PMID: 30660654
DOI: 10.1016/j.fitote.2018.12.026

Abstract

A new bisindole alkaloid, melosuavine I (1) possessing an aspidosperma-aspidosperma dimeric skeleton, was isolated from the leaves of Melodinus suaveolens. The structure with absolute configuration of 1 was elucidated by a combination of MS, NMR and computational methods. MTT assays indicated that 1 exhibited significant cytotoxicity on human breast cancer BT549 cells with an IC₅₀ value of 0.89 μM. Further study showed that 1 inhibited BT549 cell proliferation by inducing apoptosis through activation of caspase 3 and p53, and down-regulation of Bcl-2.

Keywords: Anticancer; Apoptosis; Bisindole alkaloid; Melodinus suaveolens.

MeSH terms

Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Apocynaceae / chemistry*
Apoptosis / drug effects*
Caspase 3 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
China
Drug Screening Assays, Antitumor
Humans
Indole Alkaloids / isolation & purification
Indole Alkaloids / pharmacology*
Molecular Structure
Phytochemicals / isolation & purification
Phytochemicals / pharmacology
Plant Leaves / chemistry
Proto-Oncogene Proteins c-bcl-2 / metabolism
Tumor Suppressor Protein p53 / metabolism

Substances

Antineoplastic Agents, Phytogenic
BCL2 protein, human
Indole Alkaloids
Phytochemicals
Proto-Oncogene Proteins c-bcl-2
TP53 protein, human
Tumor Suppressor Protein p53
CASP3 protein, human
Caspase 3