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Structural revision of sesbagrandiflorains A and B, and synthesis and biological evaluation of 6-methoxy-2-arylbenzofuran derivatives

Abstract

Sesbagrandiflorains A (1) and B (2), isolated from the stem bark of the Indonesian fabaceous plant Sesbania grandiflora, were reported to be 6-methoxy-2-(2´,3´-dihydroxy-5´-methoxyphenyl)-1-benzofuran-3-carbaldehyde and 6-hydroxy-2-(2´,3´-dihydroxy-5´-methoxyphenyl)-1-benzofuran-3-carbaldehyde, respectively. However, based on reevaluation of their 1D and 2D NMR data, the chemical structures of 1 and 2 have been revised to 4-hydroxy-2-(4´-hydroxy-2´-methoxyphenyl)-6-methoxybenzofuran-3-carbaldehyde and 4-hydroxy-2-(4´-hydroxy-2´-hydroxyphenyl)-6-methoxybenzofuran-3-carbaldehyde, respectively. In addition, seven new derivatives of 1 have been synthesized from the natural product in good yields (65 − 93%). The chemical structures of the synthetic compounds—one diester (6), four ethers (7–10), one secondary amine (11), and one oxime (12)—were confirmed by MS and NMR analysis. Compound 6 exhibited moderate antibacterial activity against the plant pathogen Rhodococcus fascians with a MIC of 0.1 mg/mL. Compounds 8 and 12 demonstrated respectable cytotoxicity against A375 melanoma cancer cells line with the relative IC50 values of 22.8 and 32.7 μM, respectively.

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Acknowledgements

The authors thank the Directorate of Research and Community Services, Directorate General of Higher Education, The Ministry of Research, Technology and Higher Education, Republic of Indonesia for providing funds for this project through PSN Grant 2017-2019 (No. 860/UN26.21/PN/2019), PDUPT Grant 2019 (No. 856/UN26.21/PN/2019) and World Class Professor Program-Scheme B 2018 (No.123.44/D2.3/KP/2018). Work at Oregon State University was funded by the National Institute of Food and Agriculture of the U.S. Department of Agriculture under Award Number 2014-51181-22384 and the National Center for Complementary & Integrative Health of the National Institutes of Health under Award Number T32AT010131. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Department of Agriculture and/or the National Institutes of Health. We acknowledge the support of the Oregon State University NMR Facility funded in part by the National Institutes of Health, HEI Grant 1S10OD018518, and by the M. J. Murdock Charitable Trust grant #2014162.

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Noviany, N., Samadi, A., Carpenter, E.L. et al. Structural revision of sesbagrandiflorains A and B, and synthesis and biological evaluation of 6-methoxy-2-arylbenzofuran derivatives. J Nat Med 75, 66–75 (2021). https://doi.org/10.1007/s11418-020-01445-2

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Keywords

  • Antibacterial activity
  • Cytotoxicity
  • sesbagrandiflorain
  • Sesbania grandiflora
  • Rhodococcus fascians