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ARS Home » Pacific West Area » Hilo, Hawaii » Daniel K. Inouye U.S. Pacific Basin Agricultural Research Center » Tropical Plant Genetic Resources and Disease Research » Research » Publications at this Location » Publication #411966
Research Project: Crop Health and Genetic Improvement of Sub-Tropical and Tropical Crops in the Pacific

Location: Tropical Plant Genetic Resources and Disease Research

Title: Bioassay-guided isolation and identification of cytotoxic compounds from Melaleuca quinquenervia fruits

Author
item RAKSAT, ACHARA - University Of Hawaii
item ATANU, MD SAMIUL HUQ - University Of Hawaii
item MENDEZ, SHEYANNE - University Of Hawaii
item DE LA ZERDA, RAFAEL - University Of Hawaii
item SUN, RUI - University Of Hawaii
item CHEENPRACHA, SAROT - University Of Phayao
item Wall, Marisa
item SIMMONS, CHARLES - University Of Hawaii
item WILLIAMS, PHILIP - University Of Hawaii
item TAN, GHEE - University Of Hawaii
item WONGWIWATTHANANUKIT, SUPAKIT - University Of Hawaii
item CHANG, LENG CHEE - University Of Hawaii

Submitted to: ACS Omega
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2024
Publication Date: 4/23/2024
Citation: Raksat, A., Atanu, M., Mendez, S., de la Zerda, R., Sun, R., Cheenpracha, S., Wall, M.M., Simmons, C.J., Williams, P.G., Tan, G.T., Wongwiwatthananukit, S., Chang, L. 2024. Bioassay-guided isolation and identification of cytotoxic compounds from Melaleuca quinquenervia fruits. ACS Omega. 9(16):17691-18687. https://doi.org/10.1021/acsomega.4c00769.
DOI: https://doi.org/10.1021/acsomega.4c00769

Interpretive Summary: Melaleuca quinquenervia (the broad leaf paperbark tree) is a resilient evergreen species found in tropical and subtropical regions. The leaves of M. quinquenervia (Mq) have been used in folk medicine for the treatment of microbial infections, gastrointestinal disorders, and skin lesions. In this study, bioassay-guided fractionation was used to isolate and identify the bioactive constituents within Mq fruit extract. A total of 19 compounds were successfully isolated, comprising three new flavonoids and 16 known compounds. One of the compounds, pyracrenic acid, was 2.6-fold more cytotoxic towards lung cancer cells compared to non-tumorigenic cells. This level of selectivity approaches that of the chemotherapeutic drug, cisplatin. These findings suggest that the compounds isolated may be further developed with a view to improving their selectivity and potential as lead compounds for anticancer drug discovery.

Technical Abstract: The bioassay-guided fractionation of the fruit extract of Melaleuca quinquenervia (Myrtaceae) resulted in the isolation of novel spiro-biflavonoid enantiomers (1a and 1b) and a chalcone derivative (3), along with 15 known compounds (2 and 4–17). The new compounds were structurally characterized through comprehensive spectroscopic analysis. The racemic mixture of 1 was successfully resolved into enantiomers, (+)-1 and (-)-1 by chiral-phase HPLC. Single-crystal X-ray diffraction analysis confirmed the structure of 1. Enantiomeric configurations of 1 and 2 were determined by comparing calculated and experimental ECD spectra. The cytotoxic effect of the crude extract, fractions and isolated compounds were determined using a sulforhodamine B (SRB) cytotoxicity assay in A549 non-small cell lung cancer (NSCLC) cell line. Compounds 2 (melanervin), 14 (methyl betulinate), 15 (3-O-acetylbetulinic acid), and 16 (pyracrenic acid) exhibited potent cytotoxic effect. Notably, compound 16 demonstrated superior growth inhibition of A549 cells (IC50 2.8 ± 0.1 µM) compared to the positive control chemotherapeutic drug, cisplatin (IC50 3.3 ± 0.03 µM). Furthermore, compound 16 and cisplatin were 2.6- and 3.0-fold more cytotoxic towards A549 lung cancer cells compared to non-tumorigenic Vero E6, respectively.