Jintapat NateewattanaRungnapha SaeengSakkasem KasemsookKanoknetr SuksenSuman DuttaSurawat JariyawatArthit ChairoungduaApichart SuksamrarnPawinee PiyachaturawatMahidol UniversityBurapha UniversityRamkhamhaeng University2018-10-192018-10-192013-04-01Investigational New Drugs. Vol.31, No.2 (2013), 320-33215730646016769972-s2.0-84879551946https://repository.li.mahidol.ac.th/handle/20.500.14594/32418Summary: Topoisomerase II α enzyme plays a critical role in DNA replication process. It controls the topologic states of DNA during transcription and is essential for cell proliferation. Human DNA topoisomerase II α (hTopo II α) is a promising chemotherapeutic target for anticancer agents against a variety of cancer types. In the present study, andrographolide and its structurally modified analogues were investigated for their inhibitory activities on hTopo II α enzyme. Five out of nine andrographolide analogues potently reduced hTopo II α activity and inhibited cell proliferation in four mammalian cell lines (Hela, CHO, BCA-1 and HepG2 cells). IC50values for cytotoxicity of analogues 3A.1, 3A.2, 3A.3, 1B and 2C were 4 to 7 μM. Structure-activity relationship studies revealed that both core structure of andrographolide and silicon based molecule of functional group were important for the inhibition of hTopo II α activity whereas position C-19 of analogues was required for anti-proliferation. In addition, the analogue 2C at 10 μM concentration inhibited hTopo II α, and induced apoptosis with nuclear fragmentation and formation of apoptotic bodies in HepG2 cells. The analogue 2C may, therefore, have a therapeutic potential as effective anticancer agent targeting the hTopo II α functions. © 2012 Springer Science+Business Media, LLC.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1007/s10637-012-9868-9