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Open AccessArticle

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

1
Research Institute of Medicine & Pharmacy, Qiqihar Medical University, Qiqihar 161006, China
2
College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China
3
Basic Medical Science College, Qiqihar Medical University, Qiqihar 161006, China
*
Author to whom correspondence should be addressed.
Molecules 2020, 25(5), 1209; https://doi.org/10.3390/molecules25051209
Received: 6 February 2020 / Revised: 2 March 2020 / Accepted: 6 March 2020 / Published: 7 March 2020
(This article belongs to the Section Medicinal Chemistry)
A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7ag) or thiosemicarbazone (7hk) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy. View Full-Text
Keywords: ergosterol peroxide; semicarbazone; thiosemicarbazone; anti-tumor activity; apoptosis; HepG2 cells ergosterol peroxide; semicarbazone; thiosemicarbazone; anti-tumor activity; apoptosis; HepG2 cells
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MDPI and ACS Style

Ma, L.; Wang, H.; Wang, J.; Liu, L.; Zhang, S.; Bu, M. Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies. Molecules 2020, 25, 1209.

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