Synthesis and evaluation of new sterol derivatives as potential antitumor agents

Chen, Xiang; Gan, Yong; Yu, Yu; Zhang, Yuan

doi:10.1039/c8ra04152k

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…Similarly, our group previously reported a novel isoquinoline derivative, TNBG (Figure ), which exhibits good inhibitory potencies on many human cancer cell lines and shows no cross-resistance with many other antitumor drugs in vitro. − Specifically, TNBG -induced lipid accumulation in cancer cells, which may be associated with PPARγ . However, the solubility of TNBG did not meet the criteria as a good candidate compound.…”

Section: Introductionmentioning

confidence: 99%

Tetrazanbigen Derivatives as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Partial Agonists: Design, Synthesis, Structure–Activity Relationship, and Anticancer Activities

et al. 2021

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Tetrazanbigen (TNBG) is a novel sterol isoquinoline derivative with poor water solubility and moderate inhibitory effects on human cancer cell lines via lipoapoptosis induction. Herein, we developed a series of novel TNBG analogues with improved water solubility and antiproliferative activities. The CCK-8 assay enabled us to identify a novel compound, 14g, which strongly inhibited HepG2 and A549 cell growth with IC 50 values of 0.54 and 0.47 μM, respectively. The anticancer effects might be explained by the partial activation and upregulation of PPARγ expression, as indicated by the transactivation assay and western blotting evaluation. Furthermore, the in vitro antiproliferative activity was verified in an in vivo xenograft model in which 14g strongly reduced tumor growth at a dose of 10 mg/kg. In line with these positive observations, 14g exhibited an excellent water solubility of 31.4 mg/mL, which was more than 1000-fold higher than that of TNBG (4 μg/mL). Together, these results suggest that 14g is a promising anticancer therapeutic that deserves further investigation.

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Section: Introductionmentioning

confidence: 99%

Tetrazanbigen Derivatives as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Partial Agonists: Design, Synthesis, Structure–Activity Relationship, and Anticancer Activities

et al. 2021

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“…[1] Therefore, newer approaches to treat cancer and explorations on the mechanism of cancer growth are in continuous demand. [2,3] Recently, the development of novel anticancer drugs has mainly focused on molecularly targeted therapeutics, [4,5] but the conventional approach [6][7][8][9] based on screening of cytotoxic agents in multiple human tumor cell lines remains the most successful method.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of substituted pyrrolidines and pyrroles as potential anticancer agents

Sajjad

You

et al. 2020

Archiv der Pharmazie

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A series of polysubstituted pyrrolidines obtained via ruthenium-catalyzed cascade cyclization of diazo pyruvates and anilines as well as their corresponding pyrrole analogs obtained via dehydration were evaluated for their antiproliferation activities. Pyrrolidines 3h and 3k showed good proliferation inhibitory effects toward 10 cancer cell lines with IC 50 values ranging from 2.9 to 16 μM. Furthermore, pyrrolidine 3k induced cell cycle arrest at the G0/G1 phase and time-and dose-dependent cellular apoptosis in both HCT116 and HL60 cells, suggesting that this type of pyrrolidine structure might be a good candidate for future anticancer therapies.

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“…Our preliminary study suggests that TNBG-5602 can inhibit the proliferation of many cancer cells in vitro. [22] The aim of this study was to confirm the anticancer effect of TNBG-5602 in vitro and in vivo and investigate the underlying mechanism. First, we demonstrated the antiproliferation effect of TNBG-5602 in liver cancer cells QGY-7701 using a CCK-8 assay.…”

Section: Discussionmentioning

confidence: 99%

“…Our preliminary study suggests that TNBG‐5602 can inhibit the proliferation of many cancer cells in vitro . The aim of this study was to confirm the anticancer effect of TNBG‐5602 in vitro and in vivo and investigate the underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a series of TNBG derivatives were designed and synthesized to improve its water solubility while maintaining or increasing the anticancer activity. Among these derivatives, compound 2a (named TNBG‐5602, the structure is shown in Figure ) showed good water solubility and strong antiproliferative effect in many cancer cells . The results of our previous study suggested that TNBG‐5602 may be a potential anticancer drug and prompted us to study its anticancer mechanism.…”

Section: Introductionmentioning

confidence: 99%

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TNBG-5602, a novel derivative of quinoxaline, inhibits liver cancer growth via upregulating peroxisome proliferator-activated receptor γ in vitro and in vivo

Wan

Zhang

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives TNBG‐5602 is a newly synthesized compound with an isoquinoline structure. In the present study, we demonstrated the anticancer effect of TNBG‐5602 in in‐vitro and in‐vivo models and investigated its possible anticancer mechanism. Methods The antiproliferation effect of TNBG‐5602 in vitro was evaluated in human liver cancer cell line QGY‐7701. The acute toxicity of TNBG‐5602 was evaluated in mice. The anticancer activity of TNBG‐5602 in vivo was assessed in a xenograft model of human liver cancer cell line QGY‐7701. Key findings The results of CCK‐8 assay showed that TNBG‐5602 can effectively inhibit the proliferation of liver cancer cells in vitro. The acute toxicity test in mice showed that the LD50 of TNBG‐5602 was 172 mg/kg. In a xenograft liver cancer model, TNBG‐5602 could remarkably inhibit the growth of tumours. During in‐vitro and in‐vivo studies, we noted that TNBG‐5602 could induce lipid accumulation in cancer cells and tissues. Further study indicated that the anticancer effect of TNBG‐5602 may be exerted through activating peroxisome proliferator‐activated receptor γ (PPARγ) and downregulating proliferating cell nuclear antigen (PCNA). Conclusions Our results suggested that TNBG‐5602 might exert potent anticancer activity through increasing the expression of PPARγ.

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Synthesis and evaluation of new sterol derivatives as potential antitumor agents

Abstract: The current optimization of tetrazanbigen (TNBG) on the C-ring provided a series of new sterol derivatives 2a-2n. All new synthesized compounds were screened for their anti-proliferation activities against five

Cited by 11 publications

References 27 publications

Tetrazanbigen Derivatives as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Partial Agonists: Design, Synthesis, Structure–Activity Relationship, and Anticancer Activities

Tetrazanbigen Derivatives as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Partial Agonists: Design, Synthesis, Structure–Activity Relationship, and Anticancer Activities

Synthesis and biological evaluation of substituted pyrrolidines and pyrroles as potential anticancer agents

TNBG-5602, a novel derivative of quinoxaline, inhibits liver cancer growth via upregulating peroxisome proliferator-activated receptor γ in vitro and in vivo

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