Cytotoxic lignans from the roots and rhizomes of Diphylleia sinensis, a China’s endemic plant species

Abstract

Eight novel arylnaphthalide lactone lignans, designated as diphylignan A−H (1−8), and a new dibenzyltyrolactone lignan, designated as diphylignan I (9), were isolated from the roots and rhizomes of Diphylleia sinensis, along with two additional novel natural products (11 and 14) and four known metabolites (10, 12, 13, 15). The structural and stereochemical characterization of these compounds was accomplished using NMR spectroscopy and electronic circular dichroism (ECD) analysis. The cytotoxic activities of all isolated compounds were assessed against A-549 and SMMC-7721 cell lines. Notably, compound 2 demonstrated the most significant cytotoxicity, with IC₅₀ values of 10.27 and 11.58 µmol·L⁻¹ against A-549 and SMMC-7721 cell lines, respectively, exhibiting greater potency than the positive control, cisplatin.

Keywords

Diphylleia sinensis / Dibenzyltyrolactone / Arylnaphthalide / Cytotoxic

References

[1] Broomhead AJ, Dewick PM. Tumor-​inhibitory aryltetralin lignans in Podophyllum versipelle, Diphylleia cymosa and Diphylleia grayi[J]. Phytochemistry, 1990, 29(12): 3831-3837.

[2] Zhao CL, Zhang N, He WY, et al. Simultaneous determination of three major lignans in rat plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Diphylleia sinensis extract[J]. Biomed Chromatogr, 2014, 28(4): 463-467.

[3] Zhao W, Cong Y, Li HM, et al. Challenges and potential for improving the druggability of podophyllotoxin-derived drugs in cancer chemotherapy[J]. Nat Prod Rep, 2021, 38(3): 470-488.

[4] Toussie BT, Nguengang RT, Mawabo IK, et al. Bioactive arylnaphthalide lignans from Justicia depauperata[J]. J Nat Prod, 2022, 85(12): 2731-2739.

[5] Sun YJ, Li ZL, Chen H, et al. Three new cytotoxic aryltetralin lignans from Sinopodophyllum emodi[J]. Bioorg Med Chem Lett, 2011, 21(12): 3794-3797.

[6] Zheng XK, Cao YG, Ke YY, et al. Phenolic constituents from the root bark of Morus alba L. and their cardioprotective activity in vitro[J]. Phytochemistry, 2017, 135: 128-134.

[7] Kim HJ, Kim SH, Kang BY, et al. Microbial metabolites of 8-prenylnaringenin, an estrogenic prenylflavanone[J]. Arch Pharm Res, 2008, 31(10): 1241-1246.

[8] Zhou H, Yang YB, Liu Y, et al. Chemical constituents from the fermentation broth of Streptomyces sp. (yim69228)[J]. Nat Prod Res Dev, 2013, 25(3): 293-295.

[9] Feliciano AS, Corral JMMD, Gordaliza M, et al. Acetylated lignans from Juniperus sabina[J]. Phytochemistry, 1989, 28(2): 659-660.

[10] Ibrahim MA, Rodenburg DL, Alves K, et al. Rebaudiosides R and S, minor diterpene glycosides from the leaves of Stevia rebaudiana[J]. J Nat Prod, 2016, 79(5): 1468-1472.

[11] Estevez-Braun A, Estevez-Reyes R, Gonzalez AG. ¹³C NMR assignments of some dibenzyl-γ-butyrolactone lignans[J]. Phytochemistry, 1996, 43(4): 885-886.

[12] Luo SQ, Lin LZ, Cordell GA. Lignan glucosides from Bupleurum wenchuanense[J]. Phytochemistry, 1993, 33(1): 193-196.

[13] Delcorral JMM, Gordaliza M, Castro MA, et al. Methyl ethers of podophyllotoxin-related cyclolignans[J]. J Nat Prod, 1995, 58(6): 870-877.

[14] Rajapaksa D, Rodrigo R. A stereocontrolled synthesis of antineoplastic podophyllum lignans[J]. J Am Chem Soc, 1981, 103(20): 6208-6209.

[15] Zhao CQ, Nagatsu A, Hatano K, et al. New lignan glycosides from Chinese medicinal plant, Sinopodophillum emodi[J]. Chem Pharm Bull, 2003, 51(3): 255-261.

[16] Sun YJ, Pan RY, Chen HJ, et al. Cytotoxic polyhydroxylated oleanane triterpenoids from Cissampelos pareira var. hirsuta[J]. Molecules, 2022, 27: 1183.

Funding

Key Research Project of Higher Education Institution in Henan Province(24A360015)

Scientific and Technological Key Project in Henan Province(192102310438)

Program for Innovative Research Team (in Science and Technology) in University of Henan Province(24IRTSTHN039)

Research Project on Chinese Medicine Science in Henan Province(20-21ZY1039)