Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors

Sever, Belgin; Altıntop, Mehlika Dilek; Radwan, Mohamed O.; Özdemır, Ahmet; Otsuka, Masami; Fujita, Mikako; Çiftçi, Halil

doi:10.1016/j.ejmech.2019.111648

Cited by 74 publications

(32 citation statements)

References 51 publications

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“…The stock solution of compounds and imatinib (Wako Pure Chemical Industries) in concentrations between 3 and 30 mM was prepared in dimethyl sulfoxide (DMSO; Wako Pure Chemical Industries) and then was added to the fresh culture medium. The concentration of DMSO in the final culture medium was 1% (Sever et al, ).…”

Section: Methodsmentioning

confidence: 99%

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

et al. 2020

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Herein, we report the synthesis and cytotoxic effects of novel chlorinated plastoquinone analogs (ABQ1–17) against different leukemic cells. Compounds ABQ3, ABQ11, and ABQ12 demonstrated a pronounced antiproliferative effect against chronic myelogenous leukemia (CML) K562 cell line with IC50 values of 0.82 ± 0.07, 0.28 ± 0.03, and 0.98 ± 0.22 μM, respectively. Among them, ABQ11 showed approximately three times higher selectivity than imatinib on CML. ABQ11‐treated CML cells induced significant apoptosis at low concentration. Inhibitory effect of ABQ11 against eight different tyrosine kinases, including ABL1, was investigated. ABQ11 inhibited ABL1 with IC50 value of 13.12 ± 1.71 μM, indicating that the moderate inhibition of ABL1 kinase is just an in‐part mechanism of its outstanding cellular activity. Molecular docking of ABQ11 into ABL1 kinase ATP‐binding pocket revealed the formation of some key interactions. Furthermore, DNA cleavage assay showed that ABQ11 strongly disintegrated DNA at 1 μM concentration in the presence of iron (II) complex system, assuming that the major mechanism for the anticancer effects of ABQ11 is DNA cleavage. In silico ADMET prediction revealed that ABQ11 is a drug‐like small molecule with a favorable safety profile. Taken together, ABQ11 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from imatinib.

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Section: Methodsmentioning

confidence: 99%

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

et al. 2020

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“…The latter showed the most potent activity by far (IC50 = 1.70 μM for compound 46) ( Figure 17). The activity was dependent on the substituent at the 4-position Recently, Altintop et al reported the synthesis and evaluation of a library of 26 thiazolyl-pyrazoline hybrids as dual EGFR and HER2 inhibitors, incorporating the morpholine or piperidine ring as well [112]. The morpholine bearing derivative 44 ( Figure 16) showed both the highest EGFR and HER2 inhibitory activity with IC 50 values of 4.34 and 2.28 µM.…”

Section: Thiazole and Benzothiazole Pyrazoline Hybridsmentioning

confidence: 99%

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

Matiadis

Sagnou

2020

IJMS

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Pyrazolines are five-membered heterocycles possessing two adjacent nitrogens. They have attracted significant attention from organic and medicinal chemists due to their potent biological activities and the numerous possibilities for structural diversification. In the last decade, they have been intensively studied as targets for potential anticancer therapeutics, producing a steady yearly rise in the number of published research articles. Many pyrazoline derivatives have shown remarkable cytotoxic activities in the form of heterocyclic or non-heterocyclic based hybrids, such as with coumarins, triazoles, and steroids. The enormous amount of related literature in the last 5 years prompted us to collect all these published data from screening against cancer cell lines, or protein targets like EGFR and structure activity relationship studies. Therefore, in the present review, a comprehensive account of the compounds containing the pyrazoline nucleus will be provided. The chemical groups and the structural modifications responsible for the activity will be highlighted. Moreover, emphasis will be given on recent examples from the literature and on the work of research groups that have played a key role in the development of this field.

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“…The wide variety of bioactivities of pyrazolines lead many researchers to synthesize new pyrazoline derivatives. Pyrazoline substituents are important target molecules for chemists because of their many potential applications, such as pharmaceuticals and the like . Some pyrazoline derivatives have been shown to exhibit pharmacological effects such as antidepressant, antibacterial, antitumor, and anti‐inflammatory activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of some new pyrazolines and their inhibitory potencies against carbonic anhydrases

Çelik

Arslan

Şentürk

et al. 2020

Archiv der Pharmazie

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The inhibition of the two human cytosolic carbonic anhydrase (hCA; EC 4.2.1.1) isozymes I and II with some new pyrazoline derivatives was investigated for the first time. The structures of the newly synthesized pyrazoline derivatives were characterized by Fourier transform‐infrared spectroscopy, 1H‐/13C‐nuclear magnetic resonance, and mass spectrometry, and elemental analysis. Compounds 1–6 showed Ki values in the range of 16.4–205.9 nM for hCA I and of 6.08–93.21 nM against hCA II. These hydroxyl and amino group‐containing compounds generally were competitive inhibitors. The compounds investigated here showed effective hCA I and II inhibitory effects, in the same range as the clinically used acetazolamide, and might be used as leads for generating enzyme inhibitors, possibly targeting other CA isoforms that have not yet been assayed for their interactions with such agents.

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Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors

Cited by 74 publications

References 51 publications

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

Pyrazoline Hybrids as Promising Anticancer Agents: An Up-to-Date Overview

Synthesis and characterization of some new pyrazolines and their inhibitory potencies against carbonic anhydrases

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