Synthesis and BK channel-opening activity of 2-amino-1,3-thiazole derivatives

Qi, Xiaobin; Jo, Heeji; Ji, Tong-Tong; Lin, Haixia; Park, Chul–Seung; Cui, Yongmei

doi:10.1016/j.bmcl.2021.128083

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…In the present study, we employed different BK channel activators [ 20 , 22 , 33 , 34 ] ( Figure 1 ) in order to explore the feasibility to modulate BK channel function to reduce cell viability, proliferation, and migration in two different cancer lines, i.e., melanoma (IGR39) and PDAC (Panc-1). As a negative control, to test whether effects were specific to BK channel activation, we utilized the IGR37 cells, as in this cell line, BK is barely expressed compared to its primary counterpart IGR39 [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…In parallel, we found that NS-19504 also favors the opening of BK channels in IGR39 and Panc-1 cells ( Figure 2 ). Instead, a third BK channel opener, BMS-191011 ( Figure 1 ) [ 22 ], showed only very poor potency: application of 20 or 40 µM BMS-191011 activated BK channels in less than 50% IGR39 cells ( Figure 4 ) and led to less than twofold potentiation in Panc-1 cells ( Figure 4 ). In addition, in IGR39 cells, BMS-191011 promoted the activation of a voltage-independent K + conductance at negative voltages ( Figure 4 B), not responsive to paxilline.…”

Section: Discussionmentioning

confidence: 99%

“…In light of the involvement of BK channel in various pathophysiological conditions, the biophysical mechanisms underlying its regulation have been extensively studied, and BK openers are sought as novel avenues to the treatment of diseases, including stroke, epilepsy, asthma, arterial ischemic heart disease, and cancer. These activators include NS-11021, NS-19504, and BMS-191011 [ 13 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

Zuccolini

Barbieri

Ferrera

et al. 2021

Cancers

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Potassium channels have emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large-conductance Ca2+-activated K+ channel, often referred to as BK channel, is involved in several cancer-associated processes. Here, we investigated the effects of different BK activators, NS-11021, NS-19504, and BMS-191011, in IGR39 (primary melanoma cell line) and Panc-1 (primary pancreatic duct carcinoma cell line), highly expressing the channel, and in IGR37 (metastatic melanoma cell line) that barely express BK. Our data showed that NS-11021 and NS-19504 potently activated BK channels in IGR39 and Panc-1 cells, while no effect on channel activation was detected in IGR37 cells. On the contrary, BK channel activator BMS-191011 was less effective. However, only NS-11021 showed significant effects in cancer-associated processes, such as cell survival, migration, and proliferation in these cancer cell lines. Moreover, NS-11021 led to an increase of intracellular Ca2+ concentration, independent of BK channel activation, thus complicating any interpretation of its role in the regulation of cancer-associated mechanisms. Overall, we conclude that the activation of the BK channel by itself is not sufficient to produce beneficial anti-cancer effects in the melanoma and PDAC cell lines examined. Importantly, our results raise an alarm flag regarding the use of presumably specific BK channel openers as anti-cancer agents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

Zuccolini

Barbieri

Ferrera

et al. 2021

Cancers

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Potassium channelopathies associated with epilepsy-related syndromes and directions for therapeutic intervention

Gribkoff

Winquist

2023

Biochemical Pharmacology

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Recent Literature on the Synthesis of Thiazole Derivatives and their Biological Activities

Farghaly

Alfaifi

Gomha

2024

MRMC

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The thiazole ring is naturally occurring and is primarily found in marine and microbial sources. It has been identified in various compounds such as peptides, vitamins (thiamine), alkaloids, epothilone, and chlorophyll. Thiazole-containing compounds are widely recognized for their antibacterial, antifungal, anti-inflammatory, antimalarial, antitubercular, antidiabetic, antioxidant, anticonvulsant, anticancer, and cardiovascular activities. The objective of this review is to present recent advancements in the discovery of biologically active thiazole derivatives, including their synthetic methods and biological effects. This review comprehensively discusses the synthesis methods of thiazole and its corresponding biological activities within a specific timeframe, from 2017 until the conclusion of 2022.

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Synthesis and BK channel-opening activity of 2-amino-1,3-thiazole derivatives

Cited by 3 publications

References 28 publications

NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

Potassium channelopathies associated with epilepsy-related syndromes and directions for therapeutic intervention

Recent Literature on the Synthesis of Thiazole Derivatives and their Biological Activities

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