Antimicrobial Isoflavans and Other Metabolites of Dalea jamesii

Abstract

The phytochemical investigation of extracts of Dalea jamesii root and aerial portions led to the isolation of ten phenolic compounds. Six previously undescribed prenylated isoflavans, summarily named ormegans A – F (1 – 6), were characterized, along with two new arylbenzofurans (7, 8), a known flavone (9), and a known chroman (10). The structures of the new compounds were deduced by NMR spectroscopy, supported by HRESI mass spectrometry. The absolute configurations of 1 – 6 were determined by circular dichroism spectroscopy. Compounds 1 – 9 exhibited in vitro antimicrobial activities, causing 98% or greater growth inhibition at concentrations as low as 2.5 – 5.1 µM against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and Cryptococcus neoformans. Interestingly, the most active compound was the dimeric arylbenzofuran 8 (> 90% growth inhibition at 2.5 µM) against both methicillin-resistant S. aureus and vancomycin-resistant E. faecalis, tenfold more active than its corresponding monomer (7).

Key words

Dalea jamesii - Fabaceae - isoflavan - arylbenzofuran - MRSA - VRE - Cryptococcus neoformans - circular dichroism

Publication History

Received: 05 October 2022

Accepted after revision: 01 January 2023

Article published online:
02 March 2023

• References

• 1 Belofsky G, Engels L, McPherson V, Nash K, Sullivan K, Torrey B, Ripley C, Coria A, Bicchieri T, Dondji B. Investigation of Dalea parryi (Fabaceae) metabolites for anthelmintic activity against the human pathogenic hookworm Ancylostoma ceylanicum . Phytochemistry 2020; 177: 112423
• 2 Peralta MA, Santi MD, Cabrera JL, Ortega MG. Dalea Genus, Chemistry, and Bioactivity Studies. In: Rahman A. ed. Studies in Natural Products Chemistry, Vol. 62. Amsterdam: Elsevier B.V.; 2019: 307-341
• 3 Kartesz JT. The Biota of North America Program (BONAP). 2015. North American Plant Atlas. Chapel Hill, N.C. [maps generated from Kartesz, J. T. 2015. Floristic Synthesis of North America, Version 1.0. Biota of North America Program (BONAP)]. Accessed December 05, 2022 at: http://bonap.net/napa/taxonmaps/genus/state/dalea
• 4 The Climate Explorer. Explore how climate is projected to change in any county in the United States. Online tool. Accessed June 17, 2022 at: https://crt-climate-explorer.nemac.org
• 5 Williams AP, Cook BI, Smerdon JE. Rapid intensification of the emerging southwestern North American megadrought in 2020–21. Nat Clim Change 2022; 12: 232-234
• 6 Belofsky G, Aronica M, Foss E, Diamond J, Santana F, Darley J, Dowd PF, Coleman CM, Ferreira D. Antimicrobial and antiinsectan phenolic metabolites of Dalea searlsiae . J Nat Prod 2014; 77: 1140-1149
• 7 Peralta MA, Calise M, Fornari MC, Ortega MG, Diez RA, Cabrera JL, Pérez C. A prenylated flavanone from Dalea elegans inhibits rhodamine 6 G efflux and reverses fluconazole-resistance in Candida albicans . Planta Med 2012; 78: 981-987
• 8 World Health Organization. Antibacterial agents in clinical development: An analysis of the antibacterial clinical development pipeline; 2019. Accessed July 10, 2022 at: https://www.who.int/publications/i/item/9789240000193
• 9 Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019.
• 10 Iyer KR, Revie NM, Fu C, Robbins N, Cowen LE. Treatment strategies for cryptococcal infection: challenges, advances and future outlook. Nature 2021; 19: 454-466
• 11 Brown NM, Goodman AL, Horner C, Jenkins A, Brown EM. Treatment of methicillin-resistant Staphylococcus aureus (MRSA): Updated guidelines from the UK. JAC Antimicrob Resist 2021; 3: dlaa114
• 12 Tanaka H, Oh-Uchi T, Etoh H, Sako M, Asai F, Fukai T, Sato M, Murata J, Tateishi Y. Isoflavanoids from roots of Erythrina zeyheri . Phytochemistry 2003; 64: 753-758
• 13 Kalli S, Araya-Cloutier C, Hagerman J, Vincken JP. Insights into the molecular properties underlying antibacterial activity of prenylated (iso) flavonoids against MRSA. Sci Rep 2021; 11: 14180
• 14 Nkengfack AE, Vouffo TW, Vardamides JC, Kouam J, Fomum ZT, Meyer M, Sterner O. Phenolic metabolites from Erythrina species. Phytochemistry 1997; 46: 573-578
• 15 Slade D, Ferreira D, Marais JPJ. Circular dichroism, a powerful tool for the assessment of absolute configuration of flavonoids. Phytochemistry 2005; 66: 2177-2215
• 16 Kim M, Kim SU, Kim Y, Han J. Absolute configurations of (±)-glabridin enantiomers. Bull Korean Chem Soc 2009; 30: 415-418
• 17 Zeng JF, Li GL, Xu X, Zhu DY. Two isoprenoid-substituted isoflavans from roots of Maackia tenuifolia. Phytochemistry 1996;43: 893–896 and the associated Corrigenda, Zeng JF, Li GL, Xu X, Zhu DY. Phytochemistry 1998; 47: 1667
• 18 Tanaka H, Sudo M, Hirata M, Sako M, Sato M, Chen IS, Fukai T. Two new isoflavonoids and a new 2-arylbenzofuran from the roots of Erythrina variegata . Heterocycles 2005; 65: 871-877
• 19 Guo H, Wang M, Zheng J, Zhang S, Shen J. Studies on chemical constituents of Epimedium brevicornum . Zhongguo Yaoxue Zazhi 2006; 41: 1060-1062
• 20 Saputri RD, Tanjung M, Tjahjandarie TS. Cytotoxic activity of quinoline alkaloids and acylphloroglucinol from the leaves of Melicope denhamii . J Phys: Conf Ser 2018; 1095: 012031
• 21 Rengaraj R, Mariappan S, Sekar U, Kamalanadhan A. Detection of vancomycin resistance among Enterococcus faecalis and Staphylococcus aureus . J Clin Diagn Res 2016; 10: DC4-DC6
• 22 Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. Wayne, PA: Clinical and Laboratory Standards Institute; 2017. Accessed February 03, 2023 at: https://clsi.org/standards/products/microbiology/documents/m100/