Dimeric Pimprinine Alkaloids From Soil-Derived Streptomyces sp. NEAU-C99.

Zhiyin Yu,Feng-Xian Yang,Li Wang,Sheng-Xiong Huang,Xiaowei Guo,Hao Jiang,Wensheng Xiang,Jian-Ping Huang,Chongxi Liu

doi:10.3389/fchem.2020.00095

Abstract

Six new pimprinine alkaloids (1–6), including four dimers, dipimprinines A–D (1–4), and two monomers, (±)-Pimprinol D (5), and pimprinone A (6), along with six known congeners (7–12), were isolated from a soil-derived actinomycete Streptomyces sp. NEAU-C99. Structures of the new compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffractions, and ECD calculations. Dipimprinines A–D (1–4) showed weak cytotoxic activities against five tumor cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW-480, with IC50 values ranging from 12.7 to 30.7 μM.

Highlights

Natural products, in particular secondary metabolites derived from actinomycetes, Gram-positive bacteria (Hoshino et al, 2018; Yang et al, 2018), such as antibiotics, enzymes, enzyme inhibitors, and other pharmacologically active agents (Sripreechasak et al, 2013), have contributed substantially to modern medical care (Onaka, 2017)
Compound 1 was obtained as yellow amorphous powder, and its molecular formula C26H22N4O2 was determined by high resolution electrospray ionization mass spectrometry (HRESIMS) data (m/z 421.1670 [M-H]−, calcd for 421.1670), corresponding to 18 degrees of unsaturation (Figure S8)
The aforementioned spectroscopic evidences suggested that compound 1 was likely a dimeric pimprinine alkaloid

Summary

Introduction

In particular secondary metabolites derived from actinomycetes, Gram-positive bacteria (Hoshino et al, 2018; Yang et al, 2018), such as antibiotics, enzymes, enzyme inhibitors, and other pharmacologically active agents (Sripreechasak et al, 2013), have contributed substantially to modern medical care (Onaka, 2017). Pimprinine is an indole alkaloid, which was first isolated from the filtrates of Streptomyces pimprina cultures in 1963 (Joshi et al, 1963). Members of this family display a range of biological activities, such as antiepileptic (Naik et al, 2001; Roy et al, 2006), platelet-aggregation-inhibitory (Miao et al, 2004), antitumor (Pettit et al, 2002), fungicidal (Zhang et al, 2012), and anti-plant-viral activities (Liu et al, 2019). We describe the isolation and structure elucidation of six new pimprinine alkaloids analogs (1–6), as well as their cytotoxic activities against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines

Methods

Results

Conclusion