Unveiling the Mechanisms of Apoptosis Induction by Deep-Sea-Derived Polyketide-Terpenoid Hybrids from Penicillium allii-sativi: A Focus on Mitochondrial and mTOR Pathways
Chun-Lan Xie , Tai-Zong Wu , Duo Zhang , Yuan Wang , Ting Lin , Hai-Feng Chen , Xiao-Kun Zhang , Xian-Wen Yang
Chinese Journal of Chemistry ›› 2024, Vol. 42 ›› Issue (24) : 3283 -3292.
Unveiling the Mechanisms of Apoptosis Induction by Deep-Sea-Derived Polyketide-Terpenoid Hybrids from Penicillium allii-sativi: A Focus on Mitochondrial and mTOR Pathways
Comprehensive Summary:A chemical investigation of the deep-sea-derived fungus Penicillium allii-sativi MCCC 3A00580 resulted in the discovery of four new meroterpenoids ( 1— 4) and one related known co-metabolite ( 5). These meroterpenoids showcase unique carbon skeletons featuring a common drimane sesquiterpene part with highly diverse polyketide units. Particularly, compound 1 incorporates a salicylic acid moiety while 2 possesses a rare peroxide bridge in the polyketide part. The structures of new compounds were assigned by extensive spectroscopic analysis, quantum calculations, and biogenetic considerations. Notably, 3 significantly blocked the mTOR signaling pathway, resulting in the arrest of cell cycle at G0-G1 phase and triggering mitochondrial apoptosis in Hela cells. While the previously reported co-metabolite macrophorin A (MPA) effectively triggered cell death in MDA-MB-231 cancer cells by activating apoptosis pathways involving death receptors, mitochondria, mTOR, and TNF.
Deep-sea-derived fungus / Penicillium allii-sativi / Meroterpenoids / Drimane sesquiterpene / Peroxide / Mitochondrial apoptosis / mTOR / Cancer treatment / Terpenoid / Structure elucidation
2024 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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