N-Aryl-N′-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: Screening, synthesis of simplified derivatives, and structure–activity relationship analysis

Goffin, Eric; Lamoral-Theys, Delphine; Tajeddine, Nicolas; Tullio, Pascal De; Mondin, Ludivine; Lefranc, Florence; Gailly, Philippe; Rogister, Bernard; Kiss, Róbert; Pirotte, Bernard

doi:10.1016/j.ejmech.2012.06.050

Cited by 30 publications

(14 citation statements)

References 41 publications

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“…The presence of the tetramethylchromanol skeleton in compound MK61 is probably related with its strongest activity. This is also in agreement with other reports that describe the high antitumor activity of compounds with this skeleton in their structure . On the other hand, the antitumor activity showed by compounds MK149 and MK150 seems to be related with the presence of 1,2‐dimethoxyphenyl pharmacophores.…”

Section: Resultssupporting

confidence: 93%

Antimicrobial/Antibiofilm Activity and Cytotoxic Studies of β‐Thujaplicin Derivatives

Fotopoulou

Ćirić

Kritsi

et al. 2016

Archiv der Pharmazie

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Natural β-thujaplicin displays a remarkable array of biological activities for the prevention or treatment of various disorders while its tropolone scaffold inspired the synthesis of new analogs. The main goal of the current study was to evaluate the influence of 4-substituted piperazine moieties at position 7 of the β-thujaplicin scaffold, on the antimicrobial activity. In order to determine the biological activity of the β-thujaplicin derivatives, a microdilution method was used against a wide variety of bacteria and fungi. Pseudomonas aeruginosa PAO 1 was used for testing antiquorum and antibiofilm effects. Four human tumor cell lines (MCF-7, NCI-H460, HeLa, and HepG2) and a porcine liver derived cell line (PLP2) were used for testing antitumor and cytotoxic activity. The compounds present better antibacterial and antifungal activity in comparison with approved antimicrobials used as control agents. β-Thujaplicin showed strong antibacterial and antifungal activities against all tested species. Further studies of their antibacterial activity revealed that all compounds presented good antibiofilm and antiquorum effects. Fungi were more susceptible than bacteria to the tested compounds, with the exception of MK150, which possessed the best antibacterial effect. None of the tested compounds, at the GI50 values obtained for the tumor cell lines, have shown toxicity for non-tumor liver cells (PLP2). The prediction of physicochemical properties of the compounds was performed to further explain the structure-activity relationship. Finally, in order to explore a possible mechanism of action of the synthesized compounds, molecular docking studies were performed on CYP51 (14-a lanosterol demethylase), an important component of the fungal cell membrane.

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Section: Resultssupporting

confidence: 93%

Antimicrobial/Antibiofilm Activity and Cytotoxic Studies of β‐Thujaplicin Derivatives

Fotopoulou

Ćirić

Kritsi

et al. 2016

Archiv der Pharmazie

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“…Therefore, we hypothesized that induction of apoptosis should not be the primary mechanism of action of these compounds that could thus be used to combat models associated with, at least partial, intrinsic resistance to pro-apoptotic stimuli. If at first glance, DBHB appeared to have rather weak activity (at least in terms of IC 50 in vitro growth inhibitory concentrations), it must kept in mind that temozolomide, the most efficacious drug used clinically to treat glioblastoma [23], has IC 50 in vitro growth inhibitory concentrations ranging between 220 (U373) and 956 (Hs683) µM, depending on the glioma cell line [37]. The same features were observed for another widely used compound to combat various cancer types, i.e.…”

Section: Resultsmentioning

confidence: 99%

Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects

et al. 2013

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Bastadins-6, -9 and -16 isolated from the marine sponge Ianthella basta displayed in vitro cytostatic and/or cytotoxic effects in six human and mouse cancer cell lines. The in vitro growth inhibitory effects of these bastadins were similar in cancer cell lines sensitive to pro-apoptotic stimuli versus cancer cell lines displaying various levels of resistance to pro-apoptotic stimuli. While about ten times less toxic than the natural cyclic bastadins, the synthetically derived 5,5'-dibromohemibastadin-1 (DBHB) displayed not only in vitro growth inhibitory activity in cancer cells but also anti-angiogenic properties. At a concentration of one tenth of its in vitro growth inhibitory concentration, DBHB displayed actual antimigratory effects in mouse B16F10 melanoma cells without any sign of cytotoxicity and/or growth inhibition. The serum concentration used in the cell culture media markedly influenced the DBHB-induced antimigratory effects in the B16F10 melanoma cell population. We are currently developing a specific inhalation formulation OPEN ACCESSMolecules 2013, 18 3544 for DBHB enabling this compound to avoid plasmatic albumin binding through its direct delivery to the lungs to combat primary as well as secondary (metastases) tumors.

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“…Urea was the selected linker to replace ester function in CAPE because urea moiety contains both hydrogen bond donors and hydrogen bond acceptors, so it is prone to the formation of hydrogen bond. Several modified urea derivatives demonstrated diverse array of anti-proliferative properties (Li et al, 2010;Guagnano et al, 2011;Goffin et al, 2012;Defaux et al, 2014) e.g. sorafenib.…”

Section: Chemistrymentioning

confidence: 98%

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

Mudjupa

Abdelhamed

Refaat

et al. 2015

JAB

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Available online xxxKeywords: Caffeic acid derivatives EGFR inhibitor Triple-negative breast cancer Non-small cell lung cancer Molecular modeling Abbreviations: CA, caffeic acid CAPE, caffeic acid phenethyl ester EGFR, epidermal growth factor receptor RTK, receptor tyrosine kinase TNBC, triple-negative breast cancer a b s t r a c t A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido) vinyl)-1,2-phenylene diacetate (CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells. CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type nonsmall-cell lung cancer H460 cells with IC 50 values of 8.96 mM and 12.98 mM, respectively, these anti-proliferative effects of CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC 50 2.34 mM. The immunoblot analyses revealed that CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.

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N-Aryl-N′-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: Screening, synthesis of simplified derivatives, and structure–activity relationship analysis

Cited by 30 publications

References 41 publications

Antimicrobial/Antibiofilm Activity and Cytotoxic Studies of β‐Thujaplicin Derivatives

Antimicrobial/Antibiofilm Activity and Cytotoxic Studies of β‐Thujaplicin Derivatives

Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

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