Synthesis and Antitumor Activity of Triazole-Containing Sorafenib Analogs

Ye, Wenjing; Yao, Qi; Yu, Simiao; Gong, Ping; Qin, Mingze

doi:10.3390/molecules22101759

Cited by 13 publications

(6 citation statements)

References 24 publications

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“…Ye et al . have presented the preparation of novel triazole‐containing sorafenib scaffolds via click chemistry approach by this procedure that a solution of concentrated hydrochloride and NaNO 2 in H 2 O was added to a 0 °C solution of compounds 140 in EtOAc and the mixture was stirred to synthesize azide compounds ( 141 ).…”

Section: 4‐disubstituted‐123‐triazoles As Anti‐cancer Agentsmentioning

confidence: 99%

An Overview of Recent Advances in the Applications of Click Chemistry in the Synthesis of Bioconjugates with Anticancer Activities

Mashayekh

Shiri

2019

ChemistrySelect

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The click chemistry is one of the most powerful CÀ N bond forming-reactions towards five-membered heterocycles. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) has widely used in the discovery of anti-cancer drugs and many articles have been published in this field. This review article aims to review general mechanism aspects and the recent advances (2016-2019) of click chemistry for cancer therapy.

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Section: 4‐disubstituted‐123‐triazoles As Anti‐cancer Agentsmentioning

confidence: 99%

An Overview of Recent Advances in the Applications of Click Chemistry in the Synthesis of Bioconjugates with Anticancer Activities

Mashayekh

Shiri

2019

ChemistrySelect

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“…Furthermore, its structure is similar to amino acid histidine, leading to bio-compatibility [ 43 , 44 ], which has been proven to resist metabolism [ 4 , 45 ]. This structure also exists in a wide range of bioactive compounds including anti-cancer agents [ 4 , 37 , 46 , 47 , 48 ]. In recent years, several 1,2,3-triazole-incorporating compounds have been designed and synthesized, and they displayed good to excellent inhibitory activities toward a variety of cancer cell lines, as depicted in Figure 2 [ 4 , 31 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Section: Introductionmentioning

confidence: 99%

The Design and Synthesis of a New Series of 1,2,3-Triazole-Cored Structures Tethering Aryl Urea and Their Highly Selective Cytotoxicity toward HepG2

et al. 2022

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Target cancer drug therapy is an alternative treatment for advanced hepatocellular carcinoma (HCC) patients. However, the treatment using approved targeted drugs has encountered a number of limitations, including the poor pharmacological properties of drugs, therapy efficiency, adverse effects, and drug resistance. As a consequence, the discovery and development of anti-HCC drug structures are therefore still in high demand. Herein, we designed and synthesized a new series of 1,2,3-triazole-cored structures incorporating aryl urea as anti-HepG2 agents. Forty-nine analogs were prepared via nucleophilic addition and copper-catalyzed azide-alkyne cycloaddition (CuAAC) with excellent yields. Significantly, almost all triazole-cored analogs exhibited less cytotoxicity toward normal cells, human embryonal lung fibroblast cell MRC-5, compared to Sorafenib and Doxorubicin. Among them, 2m’ and 2e exhibited the highest selectivity indexes (SI = 14.7 and 12.2), which were ca. 4.4- and 3.7-fold superior to that of Sorafenib (SI = 3.30) and ca. 3.8- and 3.2-fold superior to that of Doxorubicin (SI = 3.83), respectively. Additionally, excellent inhibitory activity against hepatocellular carcinoma HepG2, comparable to Sorafenib, was still maintained. A cell-cycle analysis and apoptosis induction study suggested that 2m’ and 2e likely share a similar mechanism of action to Sorafenib. Furthermore, compounds 2m’ and 2e exhibit appropriate drug-likeness, analyzed by SwissADME. With their excellent anti-HepG2 activity, improved selectivity indexes, and appropriate druggability, the triazole-cored analogs 2m’ and 2e are suggested to be promising candidates for development as targeted cancer agents and drugs used in combination therapy for the treatment of HCC.

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“…The antitumor activity of kinase inhibitors containing a diaryl urea scaffold has been gaining great attention as they possess a unique binding mode and obvious kinase inhibition profile [16]. Sorafenib is a well-known diarylurea multi-targeted inhibitor of several kinases including Raf, VEGFR, c-Kit and PDGFR [17].…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of New Quinoxaline Derivatives as Anticancer Agents and Apoptotic Inducers

et al. 2019

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The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds VIId, VIIIa, VIIIc, VIIIe and XVa exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound VIIIc induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound VIIIc could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line.

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Synthesis and Antitumor Activity of Triazole-Containing Sorafenib Analogs

Cited by 13 publications

References 24 publications

An Overview of Recent Advances in the Applications of Click Chemistry in the Synthesis of Bioconjugates with Anticancer Activities

An Overview of Recent Advances in the Applications of Click Chemistry in the Synthesis of Bioconjugates with Anticancer Activities

The Design and Synthesis of a New Series of 1,2,3-Triazole-Cored Structures Tethering Aryl Urea and Their Highly Selective Cytotoxicity toward HepG2

Design and Synthesis of New Quinoxaline Derivatives as Anticancer Agents and Apoptotic Inducers

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