ADMET and DMPK, Vol. 13 No. 5, 2025.
Original scientific paper
https://doi.org/10.5599/admet.2901
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
Napasorn Chabang
; School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Bangkok, Thailand
Chanikarn Wongwitayasombat
; Biomedical Science Program, Faculty of Science, Mahidol University, Bangkok, Thailand
Patoomratana Tuchinda
; Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, Thailand
Bamroong Munyoo
; Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, Thailand
Niwat Kangwanrangsan
; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand
Suradej Hongeng
; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Bodee Nutho
; Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand
Sitthivut Charoensutthivarakul
; Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand
Phongthon Kanjanasirirat
; Department of Pathobiology, Faculty of Science, Mahidol University
*
* Corresponding author.
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.
Keywords
cleistanthin A; xanthone; breast cancer; V-ATPase
Hrčak ID:
338688
URI
Publication date:
21.9.2025.
Visits: 436 *