New xanthone and chemical constituents from the aerial parts of Mallotus glomerulatus and their cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cells: Original scientific article

Phongthon Kanjanasirirat; Napasorn Chabang; Chanikarn Wongwitayasombat; Patoomratana Tuchinda; Bamroong Munyoo; Niwat Kangwanrangsan; Suradej Hongeng; Bodee Nutho; Sitthivut Charoensutthivarakul

doi:10.5599/admet.2901

Authors

Phongthon Kanjanasirirat Department of Pathobiology, Faculty of Science, Mahidol University https://orcid.org/0000-0002-1046-7152
Napasorn Chabang School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Bangkok, Thailand https://orcid.org/0009-0003-3839-7314
Chanikarn Wongwitayasombat Biomedical Science Program, Faculty of Science, Mahidol University, Bangkok, Thailand https://orcid.org/0009-0000-0422-0623
Patoomratana Tuchinda Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, Thailand https://orcid.org/0009-0008-7674-1899
Bamroong Munyoo Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, Thailand https://orcid.org/0000-0003-3927-5960
Niwat Kangwanrangsan Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand https://orcid.org/0000-0001-6090-6689
Suradej Hongeng Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand https://orcid.org/0000-0002-7376-9393
Bodee Nutho Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand https://orcid.org/0000-0003-1979-2418
Sitthivut Charoensutthivarakul Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand https://orcid.org/0000-0002-4447-3438

DOI:

https://doi.org/10.5599/admet.2901

Keywords:

cleistanthin A, xanthone, breast cancer, V-ATPase

Abstract

Background and purpose: Breast cancer remains a significant global health burden, especially in low-resource settings where standard therapies are limited. This study aimed to explore Mallotus glomerulatus, a lesser-known Thai medicinal plant, as a potential source of novel anti-breast cancer agents. Experimental approach: A phytochemical investigation of M. glomerulatus resulted in the isolation and structural characterization of a novel xanthone (Compound 1) and cleistanthin A (Compound 10) using UV, IR, NMR, and HRMS techniques. Cytotoxicity of the compounds was evaluated in vitro against MCF-7 (ER-positive) and MDA-MB-231 (triple-negative) breast cancer cell lines, along with HepG2 liver cells. Molecular docking studies were conducted to assess their interaction with vacuolar H⁺-ATPase (V-ATPase). Key results: Compound 1 demonstrated selective cytotoxicity toward MCF-7 cells, whereas cleistanthin A exhibited potent cytotoxicity against both breast cancer lines, with nanomolar IC₅₀ values and a high selectivity index (>100) for MDA-MB-231 compared to HepG2 cells. Docking analysis revealed favourable binding of both compounds at the a–c subunit interface of V-ATPase, suggesting a mechanism involving proton pump inhibition and lysosomal dysfunction. Conclusion: The findings highlight M. glomerulatus, particularly cleistanthin A, as a promising source of safe and affordable anti-breast cancer compounds with potential therapeutic value. Further studies on the mechanism and in vivo efficacy are warranted.

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