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[Display omitted] • Four undescribed seco -polyprenylated acylphloroglucinols from H. elodeoides. • A possible biosynthetic pathway of 1 – 4 from normal PAPs was proposed. • Compound 1 induced MCF-7 cell apoptosis. • Compound 1 arrested cell cycle at S phase via inducing oxidative DNA damage. Four undescribed seco -polyprenylated acylphloroglucinols (seco -PAPs), elodeoidesones A-D (1 – 4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6- seco -PAPs with fascinating 5/5 fused ring, while 2 – 4 possess a 1,2- seco -PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1 – 4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC 50 value of 7.34 μM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage. [ABSTRACT FROM AUTHOR]

[Display omitted] • 9-methyl-9 H -purine and thieno[3,2- d ]pyrimidine derivatives were designed as mTOR inhibitors. • 15i was a potent and selective mTOR inhibitor. • 15i inhibited the proliferation of cancer cells by inducing cell cycle arrest at the G0/G1 phase. • 15i could induce autophagy by activating autophagic flux. The mammalian target of rapamycin (mTOR) has been proved to be an effective target for cancer therapy. Two kinds of mTOR inhibitors, the rapalogs and mTOR kinase inhibitors (TORKi), have been developed and clinically validated in several types of malignancies. Compared with rapalogs, TORKi can exert better antitumor activity by inhibiting both mTORC1 and mTORC2, but the clinical development of current TORKi candidates has been relative slow, more TORKi with novel scaffold need to be developed to expand the current pipelines. In this study, a series of 9-methyl-9 H -purine and thieno[3, 2- d ]pyrimidine derivatives were designed, synthesized and biological evaluation. Most of these compounds exhibited good mTOR kinase inhibitory activity and selectivity over PI3Kα. Subsequent antiproliferative assay allowed us to identify the lead compound 15i , which display nanomolar to low micromolar IC 50 s against six human cancer cell lines. 15i could induce cell cycle arrest of MCF-7, PC-3 and A549 cells at the G0/G1 phase and suppress the migration and invasion of these cancer cells by suppressing the phosphorylation of AKT and P70S6 kinase. It could also regulate autophagy-related proteins to induce autophagy. Therefore, 15i would be a starting point for the development of new TORKi as anticancer drug. [ABSTRACT FROM AUTHOR]