Neolignans and Norlignans from Insect Medicine Polyphaga plancyi and Their Biological Activities

Natural Products and Bioprospecting https://doi.org/10.1007/s13659-020-00262-0 ORIGINAL ARTICLE Neolignans and Norlignans from Insect Medicine Polyphaga plancyi and Their Biological Activities Hong‑Jie Zhu2 · Te Xu1 · Yong‑Ming Yan1 · Zheng‑Chao Tu3,4 · Yong‑Xian Cheng1 Received: 3 July 2020 / Accepted: 23 August 2020 © The Author(s) 2020 Abstract Ten neolignans or norlignans (1–10) including eight new compounds were isolated from the whole bodies of Polyphaga plancyi Bolivar. Their structures were identified by spectroscopic data. Compounds 3, 4, 8, and 9 are racemates indicated by chiral HPLC analysis. Chiral separation followed by ECD calculations allowed to clarify the absolute configurations of all the antipodes. All the new compounds were evaluated for their biological properties toward extracellular matrix in rat renal proximal tubular cells, human cancer cells (K562, A549, and Huh7), EV71, ROCK2, JAK3, DDR1, and coagulation. Graphic Abstract HO HO OH OH O HO O O (+)-3 R1=OH (+)-4 R1=OCH3 HO 5 O OH OH O HO OH R1 HO O 1 R=OH 2 R=OCH3 HO R O O HO HO 6 O OH O O 7 Keywords Polyphaga plancyi · Insect medicine · Lignans · Renal protection · Anticoagulant activity In honor of Professor Jun Zhou. Hong-Jie Zhu and Te Xu have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13659-020-00262-0) contains supplementary material, which is available to authorized users. * Yong‑Xian Cheng 1 School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen 518060, People’s Republic of China 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People’s Republic of China 3 International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou 510632, People’s Republic of China 4 Drug Discovery Pipeline & Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, People’s Republic of China 13 Vol.:(0123456789) H.-J. Zhu et al. 1 Introduction was aided by electronic circular dichroism (ECD) calculations. In addition, the biological activities of all the new compounds were assessed using multiple assays. Insects are a special group of existence on the earth. Facing the changing environment, they have strong adaptability, productivity and continuity. They seem small and insignificant, but the largest number of living beings on the planet, and their presence has created a huge molecular libraries [1, 2]. The tenacious vitality of insects is highly likely to be related to their unique molecular mechanisms [2], which provides us a confidence to track their bioactive molecules. In China, the insect Polyphaga plancyi Bolivar has been used for promoting blood circulation [3]. Whereas, so far there have few reports about its chemical composition [4]. Previous studies revealed the significance of structurally novel non-peptide small molecules (NPSMs) [5–11], inspiring our further interest on insect chemistry. As far as the title species was concerned, eight new compounds and two known compounds belonging to neolignans and norlignans were isolated in this study (Fig. 1). Chiral HPLC separation was used to afford optically active isomers. Subsequent absolute configuration clarification Fig. 1  The chemical structures of compounds 1–10 2 Results and Discussion 2.1 Structure Elucidation of the Compounds Plancyin A (1) has the molecular formula C 18H18O6 deduced from analysis of its HRESIMS ([M−H]−, m/z 329.1040, calcd 329.1031), 13C NMR, and DEPT spectra, indicating 10 degrees of unsaturation. The 1H NMR spectrum (Table 1) of 1 indicates the presence of three aromatic/olefinic protons at δH 6.63 (brs, H-2), 6.82 (brs, H-4), 6.90 (brs, H-6), indicating the presence of a 1,3,5-trisubstituted benzene ring. The 13C NMR and DEPT spectra show 9 carbons ascribed to two methylene, three sp2 methine, and four quaternary carbons (one carbonyl, three olefinic including one oxygenated). Based on the molecular formula, we judged that compound 1 is a completely symmetrical structure. The 1H–1H COSY spectrum (Fig. 2) shows correlations of H-7/H-8. The HMBC correlations of H-7/C-2, C-6, C-9 (δC 176.9), HO 3 HO OH 3 3' 5 5' 1 HO 1 HO 3 OH 7 1' 7 9 5 9 5' 7' O 9' O R HO 3' 1 O 8 5' 1' 9' R1 7' O 1 R=OH 2 R=OCH3 O HO OH 3 1 1' 3' 7 HO O 7' 10 O 3 HO 5' 1 O 5 1 5 HO 3' 1' O OH 7' OH OH O OH O 3' (+)-9 HO 8' 1' (+)-8 O 5' 13 5 5 OH 7 O 7 1 9 OH 3' O 10' 9' OH 9 O 7 HO 3 7 8 HO 1' OH 9' OH 7' O O 6 HO 3 7' 9' OH 1' 7' HO 3' (+)-3 R1=OH (+)-4 R1=OCH3 5' 5 5 HO O 10 5' Neolignans and Norlignans from Insect Medicine Polyphaga plancyi Table 1  1H (600 MHz) and 13C NMR (150 MHz) data of 1–3 (δ in ppm, J in Hz, in methanol-d4) 1 No. 6.82, brs 6.90, brs 2.88, t, 7.6 2.61, t, 7.6 O 6.82, brs 6.90, brs 2.88, t, 7.6 2.61, t, 7.6 OH 1 HO HO O O O OH 3 O O O HO OH HO OH 2 HO OH O HO 4 δH 6.63, brs 6.81a, brs 6.90, brs 2.89, t, 7.5 2.60, t, 7.5 6.61, brs 6.80a, brs 6.88, brs 2.89, t, 7.5 2.64, t, 7.5 3.65, s 3 δC 144.1 115.2b 158.8 112.8c 144.1d 119.4 32.3 37.1 177.4 143.8 115.1b 158.8 112.9c 144.0d 119.4 32.0 36.6 175.2 52.1 δH 6.59, brs 6.57, dd, 8.1, 1.9 7.01, t-like 6.61, overlap 3.23, dd, 13.6, 8.8 2.84, dd, 13.6, 6.6 3.68, t-like 6.54, brs 6.62, overlap 6.65, brs 2.80, t, 7.7 2.52, t, 7.7 δC 142.5 116.9 158.2 114.1 130.2 121.3 40.8 55.3 177.7 143.9 115.0 158.9 113.7 142.4 120.5 32.3 37.1 177.4 The same symbols at the same column are interchangeable HO O 36.8 176.9 144.0 115.1 158.8 112.8 144.1 119.5 32.1 36.8 176.9 6.63, brs a,b,c,d OH 144.0 115.1 158.8 112.8 144.1 119.5 32.1 6.63, brs 8 9 1′ 2′ 3′ 4′ 5′ 6′ 7′ 8′ 9′ 10′ HO δC δH 1 2 3 4 5 6 7 HO 2 O OH HO 5 O Fig. 2  1H–1H COSY (black bond) and key HMBC (blue arrow) correlations of 1–5 H-8/C-1, and H-4/C-2, C-3 (δC 158.8), C-6 allow to establish half the structure fragment of 1. Taken together, the structure of 1 was established as shown. Plancyin B (2) has a molecular formula of C19H20O6 derived from its HREIMS (m/z 343.1193 [M−H]−, calcd for 343.1187), 13C NMR, and DEPT spectra, having 10 degrees of unsaturation. The 1H and 13C NMR data of 2 resemble those of 1, differing in that the additional existence of a methyl in 2. The HMBC correlation of H-10′ (δH 3.65, s)/C9′ (δC 175.2) indicates the connection position of the methyl group as shown. With these in hand, the structure of 2 was readily determined. Plancyin C (3) possesses a molecular formula C 18H18O6 (10 degrees of unsaturation) deduced from its negative HRESIMS at m/z 329.1036 [M−H]− (calcd for 329.1031) and NMR data. The 1H NMR spectru (...truncated)