Design, synthesis, and biological evaluation of potent 1,2,3,4-tetrahydroisoquinoline derivatives as anticancer agents targeting NF-κB signaling pathway

Sim, Seongrak; Lee, Sumi; Ko, Seungyun; Bui, Bich Phuong; Nguyen, Pauline; Cho, Jungsook; Lee, Kiho; Kang, Jong Soon; Jung, Jae‐Kyung

doi:10.1016/j.bmc.2021.116371

Cited by 6 publications

(2 citation statements)

References 33 publications

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“…To identify promising anticancer agents, a new series of THIQ derivatives 45 and 46 were designed and synthesized [44] (Figure 20). The targeted compounds were tested against different human cancer cells.…”

Section: Antibacterialmentioning

confidence: 99%

Biological Activities of Tetrahydroisoquinolines Derivatives

Jordaan

Ebenezer

2023

J. Org. Pharm. Chem.

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1,2,3,4-Tetrahydroisoquinoline (THIQ) is a common scaffold of many alkaloids isolated from several plants and mammalian species. THIQ derivatives possess a broad spectrum of biological activities, including antitumor, antitubercular, antitrypanosomal, antibacterial, anti-HIV, anti-inflammatory, anti-Alzheimer, and anticonvulsant ones.Aim. To cover updated studies on the biological properties of THIQ derivatives, as well as their structure-activity relationship (SAR), in order to highlight the effect of diverse functional groups responsible for the manifestation of the desired activity.Results and discussion. We have presented the review on biological activities of THIQ. The SAR studies show that the electron-donating, electron-withdrawing and some heterocyclic functional groups on the backbone plays a vital role in modulating the biological potential of the compounds synthesized.Conclusions. This review will help pharmaceutical researchers to synthesize novel and potent compounds containing THIQ scaffold.

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Section: Antibacterialmentioning

confidence: 99%

Biological Activities of Tetrahydroisoquinolines Derivatives

Jordaan

Ebenezer

2023

J. Org. Pharm. Chem.

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“…In addition, the chromene moiety is an important structural element in a variety of natural and synthetic pharmacologically active compounds [ 16 , 17 ]. In this context, we have designed and synthesized angularly fused heterocyclic compounds as part of our continuing efforts to develop potential anticancer agents with heterocyclic scaffolds [ 18 , 19 , 20 ]. Among the synthesized compounds, 12-methyl-8,12-dihydrobenzo[5,6]chromeno[4,3- b ]pyrazolo[3,4- h ]quinoline (YRL1091) was found to exhibit cytotoxicity with extensive cytoplasmic vacuolization, a typical feature of paraptosis, in BC cells.…”

Section: Introductionmentioning

confidence: 99%

Induction of Paraptotic Cell Death in Breast Cancer Cells by a Novel Pyrazolo[3,4-h]quinoline Derivative through ROS Production and Endoplasmic Reticulum Stress

Nguyen

Lee

et al. 2022

Antioxidants

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Chemotherapy has been a standard intervention for a variety of cancers to impede tumor growth, mainly by inducing apoptosis. However, development of resistance to this regimen has led to a growing interest and demand for drugs targeting alternative cell death modes, such as paraptosis. Here, we designed and synthesized a novel derivative of a pyrazolo[3,4-h]quinoline scaffold (YRL1091), evaluated its cytotoxic effect, and elucidated the underlying molecular mechanisms of cell death in MDA-MB-231 and MCF-7 breast cancer (BC) cells. We found that YRL1091 induced cytotoxicity in these cells with numerous cytoplasmic vacuoles, one of the distinct characteristics of paraptosis. YRL1091-treated BC cells displayed several other distinguishing features of paraptosis, excluding autophagy or apoptosis. Briefly, YRL1091-induced cell death was associated with upregulation of microtubule-associated protein 1 light chain 3B, downregulation of multifunctional adapter protein Alix, and activation of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase. Furthermore, the production of reactive oxygen species (ROS) and newly synthesized proteins were also observed, subsequently causing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress. Collectively, these results indicate that YRL1091 induces paraptosis in BC cells through ROS generation and ER stress. Therefore, YRL1091 can serve as a potential candidate for the development of a novel anticancer drug triggering paraptosis, which may provide benefit for the treatment of cancers resistant to conventional chemotherapy.

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