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

Gan, Lin-Ling; Zhang, Gan; Dan, Yanrong; Li, Yaowei; Zhang, Peiming; Chen, Shanwen; Ye, Zaijun; Wan, Chun-Mei; Hu, Xuelian; Yu, Yu

doi:10.1021/acs.jmedchem.0c01512

Cited by 12 publications

(3 citation statements)

References 55 publications

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“…An E3 ubiquitin ligase, namely, neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) interacted with the hinge and LBD of PPAR-γ. Further, it underwent ubiquitination of PPAR-γ in adipocytes, as reported by Carvalho et al [ 220 ]. The E3 ubiquitin ligase tripartite motif containing 23 (TRIM23) promotes PPAR-γ stability by inhibiting its proteasomal degradation and controlling adipocyte development.…”

Section: Ppar-γ Partial Agonists Involved In Post-transcriptional Mod...supporting

confidence: 59%

“…Their findings demonstrated that ESD-induced PPAR-γ knockdown could cause HeLa cell line death and cell cycle arrest during G2/M phase in a dose-dependent manner [ 219 ]. Gan and associates in their investigation revealed Tetrazanbigen (TNBG), a new sterol isoquinoline derivative with poor water solubility that produced mild inhibitory effects on human tumor cell lines via lipoapoptosis induction [ 220 ]. The primary goal of employing TNBG as a PPAR gamma partial agonist was to cause tumor cells to undergo lipoapoptosis.…”

Section: Ppar-γ Partial Agonists In Cancer Therapeuticsmentioning

confidence: 99%

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PPAR-γ Partial Agonists in Disease-Fate Decision with Special Reference to Cancer

Ballav

Biswas

Sahu

et al. 2022

Cells

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Peroxisome proliferator-activated receptor-γ (PPAR-γ) has emerged as one of the most extensively studied transcription factors since its discovery in 1990, highlighting its importance in the etiology and treatment of numerous diseases involving various types of cancer, type 2 diabetes mellitus, autoimmune, dermatological and cardiovascular disorders. Ligands are regarded as the key determinant for the tissue-specific activation of PPAR-γ. However, the mechanism governing this process is merely a contradictory debate which is yet to be systematically researched. Either these receptors get weakly activated by endogenous or natural ligands or leads to a direct over-activation process by synthetic ligands, serving as complete full agonists. Therefore, fine-tuning on the action of PPAR-γ and more subtle modulation can be a rewarding approach which might open new avenues for the treatment of several diseases. In the recent era, researchers have sought to develop safer partial PPAR-γ agonists in order to dodge the toxicity induced by full agonists, akin to a balanced activation. With a particular reference to cancer, this review concentrates on the therapeutic role of partial agonists, especially in cancer treatment. Additionally, a timely examination of their efficacy on various other disease-fate decisions has been also discussed.

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Section: Ppar-γ Partial Agonists Involved In Post-transcriptional Mod...supporting

confidence: 59%

Section: Ppar-γ Partial Agonists In Cancer Therapeuticsmentioning

confidence: 99%

PPAR-γ Partial Agonists in Disease-Fate Decision with Special Reference to Cancer

Ballav

Biswas

Sahu

et al. 2022

Cells

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“…Furthermore, the in vitro antiproliferative activity was performed by using an in vivo xenograft model in which analog 45a exhibited a reduction of tumor growth at a dose of 10 mg/kg. Moreover, the water solubility of the analog 45a was found to be 31.4 mg/mL, which was 1000-fold higher than that of Tetrazanbigen (4 μg/mL) ( Figure 49 ) [ 120 ].…”

Section: Recent Developments In the Medicinal Chemistry Of Pparsmentioning

confidence: 99%

Development of Heterocyclic PPAR Ligands for Potential Therapeutic Applications

et al. 2022

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The family of nuclear peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) is a set of ligand-activated transcription factors that regulate different functions in the body. Whereas activation of PPARα is known to reduce the levels of circulating triglycerides and regulate energy homeostasis, the activation of PPARγ brings about insulin sensitization and increases the metabolism of glucose. On the other hand, PPARβ when activated increases the metabolism of fatty acids. Further, these PPARs have been claimed to be utilized in various metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. A series of different heterocyclic scaffolds have been synthesized and evaluated for their ability to act as PPAR agonists. This review is a compilation of efforts on the part of medicinal chemists around the world to find novel compounds that may act as PPAR ligands along with patents in regards to PPAR ligands. The structure–activity relationship, as well as docking studies, have been documented to better understand the mechanistic investigations of various compounds, which will eventually aid in the design and development of new PPAR ligands. From the results of the structural activity relationship through the pharmacological and in silico evaluation the potency of heterocycles as PPAR ligands can be described in terms of their hydrogen bonding, hydrophobic interactions, and other interactions with PPAR.

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Recent advances on quinoxalines as target‐oriented chemotherapeutic anticancer agents through apoptosis

Nafie,

Kahwash,

Youssef

et al. 2024

Archiv der Pharmazie

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The current review outlines all possible recent synthetic platforms to quinoxaline derivatives and the potent stimulated apoptosis mechanisms targeted by anticancer therapies. The currently reported results disclosed that quinoxaline derivatives had promising anticancer potencies against a wide array of cancer cell lines, better than the reference drugs, through target inhibition. This review summarizes some potent quinoxaline derivatives with their synthesis strategies and their potential activities against various molecular targets. Quinoxalines can be considered an important scaffold for apoptosis inducers in cancer cells through inhibiting some molecular targets, so they can be further developed as target‐oriented chemotherapeutics.

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

Cited by 12 publications

References 55 publications

PPAR-γ Partial Agonists in Disease-Fate Decision with Special Reference to Cancer

PPAR-γ Partial Agonists in Disease-Fate Decision with Special Reference to Cancer

Development of Heterocyclic PPAR Ligands for Potential Therapeutic Applications

Recent advances on quinoxalines as target‐oriented chemotherapeutic anticancer agents through apoptosis

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