A close look into the biological and synthetic aspects of fused pyrazole derivatives

Li, Mei-Mei; Huang, Hui; Pu, Yiru; Tian, Wanrong; Ruan, Wenquan; Lü, Jun

doi:10.1016/j.ejmech.2022.114739

Cited by 21 publications

(11 citation statements)

References 112 publications

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“…CC is the most common malignant tumor worldwide, with the incidence and death rate increasing annually, which seriously endangers the patients’ healthcare and life quality. Although chemotherapy and drug combination therapy are generally adopted in the clinical treatment of advanced CC, toxin accumulation and drug resistance are the primary demerits in these treatments ( Li et al, 2022a ). Therefore, it is urgent to seek new anti-tumor drugs with high efficiency and low toxicity.…”

Section: Discussionmentioning

confidence: 99%

Bruceine a exerts antitumor effect against colon cancer by accumulating ROS and suppressing PI3K/Akt pathway

et al. 2023

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Bruceine A (BA), a quassic ester from bruceine javanica, regulates diverse intracellular signal transduction pathways and manifests a variety of biological activities, however, its pharmacological mechanism in treating colon cancer (CC) is unclear. In this study, we investigated the anticancer effects of BA on CC cells and the underlying mechanisms. The network pharmacology research indicated that Akt1 and Jun and PI3K/Akt pathways are the predominant targets and critical signaling pathways, respectively, for BA treatment of CC. Meanwhile, molecular docking results implied that BA could conjugate to pivotal proteins in the PI3K/Akt pathway. BA remarkably suppressed the proliferation of CC cells HCT116 and CT26 with 48-h IC50 of 26.12 and 229.26 nM, respectively, and the expression of p-PI3K/p-Akt was restrained by BA at the molecular level as verified by Western blot assay. Further mechanistic studies revealed BA impacted cell cycle-related proteins by regulating the expression of P27 (a protein bridging the PI3K/Akt signaling pathway with cycle-related proteins), arresting the cell cycle in the G2 phase, inhibiting the proliferation of HCT116 and CT26, and facilitated the apoptosis in CC cells by activating the mitochondria-associated apoptosis protein Bax and accumulating reactive oxygen species, in addition to BA apparently inhibited the migration of CC cells. Taken together, our results demonstrated that BA might be a promising chemotherapy drug in the treatment of CC.

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Section: Discussionmentioning

confidence: 99%

Bruceine a exerts antitumor effect against colon cancer by accumulating ROS and suppressing PI3K/Akt pathway

et al. 2023

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“…(Z)-N-(4- (2,3,2diazaspiro[4.4]nona-2,8-dien-6-ylidene)-4-methylbenzenesulfonamide (3e). The residue was purified by a silica gel flash chromatography (PE/EA = 15/1) giving the product 3e as a yellow solid in 80% yield (52.5 mg), mp 178.7−182.1 °C.…”

Section: ■ Conclusionmentioning

confidence: 99%

“…Most of them feature fused-pyrazole moieties. 2 For example, apixaban, sildenafil, indiplon, zaleplon, and etazolate are well-known marketed drugs. Recently, spirocyclic compounds was found to play an important role in drug discovery and development due to the incorporation of a spiro ring fusion that can impose conformational constraints to reduce the conformational entropy penalty upon binding to a protein target in a favorable geometry.…”

Section: ■ Introductionmentioning

confidence: 99%

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Chemo- and Diastereoselective Cycloisomerization/[2 + 3] Cycloaddition of Enynamides: Synthesis of Spiropyrazolines as Potential Anticancer Reagents

Fang

Zhang

et al. 2023

J. Org. Chem.

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A silver-catalyzed one-pot cycloisomerization/[2 + 3] cycloaddition of enynamides with in situ generated nitrile imines has been developed. Unlike the well-established cycloisomerization/[4 + n] cycloadditions of enynamides, this strategy provides efficient access to a new type of spiropyrazolines, which exhibit an anti-proliferation effect on multiple tumor cell lines. The compound 3u exhibits obvious anticancer activity by inducing apoptosis in RKO cells. The combination of compound 3u and an autophagy inhibitor could improve its anti-proliferation capacities.

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“…[23] Recently, OA was also taken as a parent compound to be modified structurally as its benzylidene, oxime ester, or indole derivatives, which resulted in the generation of other more potent αglucosidase inhibitors. [24 -26] Besides, the pyrazole group is also discovered to be one key pharmacophore frequently fused a variety of bioactive compounds represented by the marketed drug sildenafil, [27] and some pyrazole-fused qunazolinone, benzofuran, pyran were reported to exhibit inhibitory activity against α-glucosidase. [28][29][30] However, few pyrazole-fused OA derivatives have not been prepared, and none of them had been tested for α-glucosidase inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Substituted Pyrazole‐Fused Oleanolic Acid Derivatives as Novel Selective α‐Glucosidase Inhibitors

Gao

Liu

et al. 2023

Chemistry & Biodiversity

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A series of novel substituted pyrazole-fused oleanolic acid derivative were synthesized and evaluated as selective α-glucosidase inhibitors. Among these analogs, compounds 4a-4f exhibited more potent inhibitory activities compared with their methyl ester derivatives, and standard drugs acarbose and miglitol as well. Besides, all these analogs exhibited good selectivity towards α-glucosidase over α-amylase. Analog 4d showed potent inhibitory activity against α-glucosidase (IC 50 = 2.64 � 0.13 μM), and greater selectivity towards αglucosidase than α-amylase by ~33-fold. Inhibition kinetics showed that compound 4d was a non-competitive α-glucosidase inhibitor, which was consistent with the result of its simulation molecular docking. Moreover, the in vitro cytotoxicity of compounds 4a-4f towards hepatic LO2 and HepG2 cells was tested.

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A close look into the biological and synthetic aspects of fused pyrazole derivatives

Cited by 21 publications

References 112 publications

Bruceine a exerts antitumor effect against colon cancer by accumulating ROS and suppressing PI3K/Akt pathway

Bruceine a exerts antitumor effect against colon cancer by accumulating ROS and suppressing PI3K/Akt pathway

Chemo- and Diastereoselective Cycloisomerization/[2 + 3] Cycloaddition of Enynamides: Synthesis of Spiropyrazolines as Potential Anticancer Reagents

Synthesis and Biological Evaluation of Substituted Pyrazole‐Fused Oleanolic Acid Derivatives as Novel Selective α‐Glucosidase Inhibitors

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