Antibacterial and Cytotoxic Bridged and Ring Cleavage Angucyclinones From a Marine Streptomyces sp.

Lin Guo,Shumin Zhang,Lu Zhang,Bo Xu,Ming Liu,Zeping Xie,Zhi Li,Qiaoli Yang,Xinzhen Fu

doi:10.3389/fchem.2020.00586

Lin Guo, Shumin Zhang + Show 7 more

Open Access

https://doi.org/10.3389/fchem.2020.00586

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Abstract

Chemical investigation of a marine-derived Streptomyces sp. KCB-132, cultivated in liquid ISP2 medium, had led to the discovery of three C-ring cleavage angucyclinone N-heterocycles, pratensilins A–C, with a novel spiro indolinone-naphthofuran skeleton. Addition of 50 μM LaCl3 to the same medium and subsequent chemical analysis of this strain returned a new member of this rare class, pratensilin D (1), along with two new angucyclinone derivatives, featuring ether-bridged (2) and A-ring cleavage (3) structural properties. Their structures and absolute configurations were assigned by spectroscopic analysis, single-crystal X-ray diffractions, and equivalent circulating density (ECD) calculations. (+)- and (–)-1, a pair of enantiomeric nitrogen-containing angucyclinones, exhibited different strengths of antibacterial and cytotoxic activities.

Highlights

1H-1H COrrelation SpectroscopY (COSY) cross-peaks for H2′/H-3′/H-4′ and H-5′ along with heteronuclear multiple bond correlations (HMBCs) couplings from H-2′ to C-6′ and from H-5′ to C-1′ allowed the constitution of a second benzene ring
The last fragment was established based on 1H-1H COSY cross-signals between H-5 and H-6 in combination with HMBCs from H-5 to C-6a and C-12b and from H-6 to C4a and C-12a, resulting in a third benzene ring as ring B, which shared double bond 4a,12b with a methyl benzene moiety to fuse into a naphthalene system, as indicated by HMBCs from H-2 to C-1 and C-12b, from 3-CH3 to C-2, C-3, and C-4, and from H-4 to C-4a (Figure 2A)
No obvious correlations were observed between ring F and other ring systems in the 1H-1H COSY and HMBC spectra, which made it problematic to assign the complete structure by spectroscopic analysis

Summary

Introduction

Angucyclines and angucyclinones (sugarless) represent the largest family of type II polyketide synthase (PKS)-engineered natural products (Rohr and Thiericke, 1992; Krohn and Rohr, 1997; Kharel et al, 2012), which share a characteristic tetracyclic benz[a]anthracene core and exhibit a wide range of biological activities (Shaaban et al, 2012; Ma et al, 2015; Xie et al, 2016; Yixizhuoma et al, 2017; Liu et al, 2019; Wu et al, 2019). No obvious correlations were observed between ring F and other ring systems in the 1H-1H COSY and HMBC spectra, which made it problematic to assign the complete structure by spectroscopic analysis.

Results

Conclusion