Synthesis and Biological Evaluation of Novel Steroidal 5α,8α-Endoperoxide Derivatives with Aromatic Hydrazone Side Chain as Potential Anticancer Agents

Wang, H. J.; Bu, Ming; Wang, J.; Liu, L.; Zhang, S.

doi:10.1134/s1068162019060396

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…In our previous work, we have found that some C-17 modified derivatives of ergosterol peroxide had significant efficacy against several human carcinoma cell lines. [21][22][23] These results provide us with confidence for further structural modification of ergosterol peroxide.…”

Section: Introductionsupporting

confidence: 56%

Synthesis and Cytotoxic Activity of Novel Ergosterol Peroxide Derivatives with Acrylate or Propionate Side Chain

Zhang

et al. 2022

Natural Product Communications

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A series of novel ergosterol peroxide derivatives with acrylate or propionate side chain were synthesized. All compounds 3a-n were evaluated for their cytotoxicity against four kinds of human carcinoma cell lines (HepG2, MCF-7, HCT-116, and A549). Most of the derivatives displayed stronger cytotoxicity than ergosterol peroxide parent. Among them, compound 3h with the highest potency against HepG2 cell line (IC50 = 2.70 μM), which was 7.47-fold more efficacious than ergosterol peroxide. The results suggested that the introduction of acrylate or propionate side chain at C-3 position of ergosterol peroxide is beneficial to enhance its cytotoxic activity. Compound 3h has potential to become a novel anti-tumor agent through further structural modification.

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Section: Introductionsupporting

confidence: 56%

Synthesis and Cytotoxic Activity of Novel Ergosterol Peroxide Derivatives with Acrylate or Propionate Side Chain

Zhang

et al. 2022

Natural Product Communications

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“…Then we synthesized several series of steroidal 5α,8α-endoperoxide derivatives with 17-(O-carboxymethyl)oxime side-chain and hydrazone hybrid side-chain. The MTT assay indicated that some derivatives possessing the 5α,8α-peroxy group and different side chains displayed distinct cytotoxic activity against some cancer cell lines [23][24][25][26][27]. Based on the above results, we speculate that the difference between side chains at C-17 position and 5α,8α-peroxy group would provide a synergistic effect for the bioactivity.…”

Section: Introductionmentioning

confidence: 68%

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

Wang

et al. 2020

Molecules

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A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) 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.

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“…Previously, we prepared a series of C-17 modified derivatives of EP (1), and many of them exhibited strong inhibitory efficacy against different kinds of tested tumor cell lines. [28][29][30][31] In addition, esterification at C-3 of EP (1) as acrylate or propionate ester has strong efficacy against 3 kinds of human tumor cell lines (Figure 3). 32 We also successfully introduced the carbamate side chain into the C-3 hydroxy group of EP (1), and most of these synthetic derivatives exhibited nanomole cytotoxic activity (Figure 3).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticancer Activity of Ergosterol Peroxide Hybrids With Paclitaxel Side Chain Inducing Apoptosis in Human Hepatoma Carcinoma Cells

Guo

Ren

et al. 2023

Natural Product Communications

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The antitumor activities of natural paclitaxel (PTX), semisynthetic docetaxel, and cabazitaxel are highly dependent on their C-13 side chains. Therefore, using natural ergosterol peroxide (EP, 1) as the lead compound, two EP-PTX hybrids (EP-A2 and EP-B2) were prepared and their antitumor activities were evaluated against 4 kinds of human MCF-7, HepG2, HCT-116, and A549 cell lines in vitro. The results showed that both EP-A2 and EP-B2 inhibited the growth of all four kinds of tested tumor cell lines. For paclitaxel-resistant MCF-7 cells, both EP-A2 and EP-B2 showed significant inhibitory activity with relatively low IC50 values (9.39 μM and 8.60 μM, respectively). In addition, EP-B2 inhibited the growth of the HepG2 cells (IC50 = 7.82 μM) more successfully than EP. Preliminary studies of the mechanism suggest that EP-B2 could arrest the G1 phase transition in HepG2 cells. In addition, EP-B2 showed an obvious apoptosis-inducing effect in HepG2 cells, as detected by the Annexin V/PI binding assay and the Western blot assay. Hybrid EP-B2 has the potential to become a novel antitumor drug through further study of the mechanism of action and its structural modifications.

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Synthesis and Biological Evaluation of Novel Steroidal 5α,8α-Endoperoxide Derivatives with Aromatic Hydrazone Side Chain as Potential Anticancer Agents

Cited by 8 publications

References 26 publications

Synthesis and Cytotoxic Activity of Novel Ergosterol Peroxide Derivatives with Acrylate or Propionate Side Chain

Synthesis and Cytotoxic Activity of Novel Ergosterol Peroxide Derivatives with Acrylate or Propionate Side Chain

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

Synthesis and Anticancer Activity of Ergosterol Peroxide Hybrids With Paclitaxel Side Chain Inducing Apoptosis in Human Hepatoma Carcinoma Cells

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