Exploring the potential intracellular targets of vascular normalization based on active candidates

Shan, Yuanyuan; Wang, Jin; Si, Ru; Ma, Yingqun; Li, Jing; Zhang, Qingqing; Liu, Wen; Zhang, Jie

doi:10.1016/j.bioorg.2020.104551

Cited by 7 publications

(6 citation statements)

References 18 publications

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“… Some 1,2,3-triazole-containing analogs with their kinase-inhibitory and anti-cancer activities [ 4 , 31 , 49 , 50 , 51 , 52 , 53 ]. …”

Section: Figures Schemes and Tablesmentioning

confidence: 99%

“…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 ]. Recently, our group also demonstrated that the triazole-containing analogs obviously had inhibitory activity against hepatocellular carcinoma cell line Huh7 with a high selectivity index (SI).…”

Section: Introductionmentioning

confidence: 99%

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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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“… Some 1,2,3-triazole-containing analogs with their kinase-inhibitory and anti-cancer activities [ 4 , 31 , 49 , 50 , 51 , 52 , 53 ]. …”

Section: Figures Schemes and Tablesmentioning

confidence: 99%

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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“…and iodine (1.3 Eq.) were sequentially added at 0 • C, according to the method descried in the literature [118][119][120]. The resulting mixture was stirred at room temperature for 6 h and reaction was quenched by addition of 10 mL of saturated aqueous Na 2 S 2 O 3 solution.…”

Section: General Procedures For the Synthesis Of The (Halidealkyl)phenoxy Nitrates (5a-p)mentioning

confidence: 99%

Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold

Sava

Buron

Routier

et al. 2021

IJMS

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Starting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, 8a-p) have been developed as a safer and more efficient multitarget therapeutic strategy. The successful synthesis of designed compounds (intermediaries and finals) was proved by complete spectroscopic analyses. In order to study the in silico interaction of NO-IND-OXDs with cyclooxygenase isoenzymes, a molecular docking study, using AutoDock 4.2.6 software, was performed. Moreover, their biological characterization, based on in vitro assays, in terms of thermal denaturation of serum proteins, antioxidant effects and the NO releasing capacity, was also performed. Based on docking results, 8k, 8l and 8m proved to be the best interaction for the COX-2 (cyclooxygense-2) target site, with an improved docking score compared with celecoxib. Referring to the thermal denaturation of serum proteins and antioxidant effects, all the tested compounds were more active than IND and aspirin, used as references. In addition, the compounds 8c, 8h, 8i, 8m, 8n and 8o showed increased capacity to release NO, which means they are safer in terms of gastrointestinal side effects.

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“…After being placed in an incubator, the cells were cultured overnight until the cells were attached. After washing the adherently grown cells three times with PBS, 200 μl of the medium was added to each well, and the corresponding reagents were added to each well as shown in Table S1, then the 24-well plates were placed in an incubator and incubated 1 h (Shan et al, 2021).…”

Section: Cell Imaging Of Ephrinb2 Mab Probesmentioning

confidence: 99%

Effective and transient mapping of protein–protein interactions: Application of novel releasable photoaffinity linkers

Wang

et al. 2021

Drug Development Research

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Herein, two novel multifunctional releasable photoaffinity linkers were developed for effective and transient tracking interacting proteins with the overall objective of understanding their in vivo biological functions in real‐time. These linkers could be used for the chemical modification of protein under moderate experimental conditions to form protein photoaffinity probes. These probes incorporated with both photoaffinity labels and tag‐transfer, enable photo‐crosslinking of bait proteins along with the release of unrelated groups. These photoaffinity linkers can be utilized to construct probes for disease markers, which could enable rapid diagnosis in a clinical setting at minimal interference with normal physiology.

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Exploring the potential intracellular targets of vascular normalization based on active candidates

Cited by 7 publications

References 18 publications

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

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, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold

Effective and transient mapping of protein–protein interactions: Application of novel releasable photoaffinity linkers

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