Chabang N.Wongwitayasombat C.Tuchinda P.Munyoo B.Kangwanrangsan N.Hongeng S.Nutho B.Charoensutthivarakul S.Kanjanasirirat P.Mahidol University2026-01-052026-01-052025-01-01Admet and Dmpk Vol.13 No.5 (2025)https://repository.li.mahidol.ac.th/handle/123456789/113789Background 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.Pharmacology, Toxicology and PharmaceuticsChemistryMedicineArticleSCOPUS10.5599/admet.29012-s2.0-10502618822718487718