scholarly journals Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2161 ◽  
Author(s):  
Yu Zhao ◽  
Tian-En Wang ◽  
Alberto Mills ◽  
Federico Gago ◽  
Wei-Shuo Fang
Keyword(s):  
Molecular Modeling ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Drug Resistant ◽  
Conformationally Constrained ◽  
Loop Region ◽  
P Glycoprotein

A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated. It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent. Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.

Jatrophane diterpenoids from the latex of Euphorbia dendroides and their anti-P-glycoprotein activity in human multi-drug resistant cancer cell lines

2013 ◽  
Vol 86 ◽  
pp. 208-217 ◽  
Author(s):  
Milka Jadranin ◽  
Milica Pešić ◽  
Ivana S. Aljančić ◽  
Slobodan M. Milosavljević ◽  
Nina M. Todorović ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Drug Resistant ◽  
P Glycoprotein

1008 Characterization of Newly Established P-glycoprotein Over-expressing Multi-drug Resistant Human Cancer Cell Lines

2012 ◽  
Vol 48 ◽  
pp. S243-S244
Author(s):  
A. Podolski-Renic ◽  
M. Pesic ◽  
M. Chiourea ◽  
J. Bankovic ◽  
T. Andjelkovic ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Drug Resistant ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
P Glycoprotein

Synthesis, Anticancer Activity on Prostate Cancer Cell Lines and Molecular Modeling Studies of Flurbiprofen-Thioether Derivatives as Potential Target of MetAP (Type II)

2020 ◽  
Vol 16 (6) ◽  
pp. 735-749 ◽  
Author(s):  
Özgür Yılmaz ◽  
Burak Bayer ◽  
Hatice Bekçi ◽  
Abdullahi I. Uba ◽  
Ahmet Cumaoğlu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Modeling ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cell Lines ◽  
Molecular Modeling Studies

Background:: Prostate cancer is still one of the serious causes of mortality and morbidity in men. Despite recent advances in anticancer therapy, there is a still need of novel agents with more efficacy and specificity in the treatment of prostate cancer. Because of its function on angiogenesis and overexpression in the prostate cancer, methionine aminopeptidase-2 (MetAP-2) has been a potential target for novel drug design recently. Objective:: A novel series of Flurbiprofen derivatives N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide (3a-c), 4-substituted-3-(1-(2-fluoro-[1,1'-biphenyl]- 4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione (4a-d), 3-(substitutedthio)-4-(substituted-phenyl)- 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-4H-1,2,4-triazole (5a-y) were synthesized. The purpose of the research was to evaluate these derivatives against MetAP-2 in vitro and in silico to obtain novel specific and effective anticancer agents against prostate cancer. Methods: The chemical structures and purities of the compounds were defined by spectral methods (1H-NMR, 13C-NMR, HR-MS and FT-IR) and elemental analysis. Anticancer activities of the compounds were evaluated in vitro by using MTS method against PC-3 and DU-143 (androgenindependent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as a positive sensitivity reference standard. Results:: Compounds 5b and 5u; 3c, 5b and 5y; 4d and 5o showed the most potent biological activity against PC3 cancer cell line (IC50= 27.1 μM, and 5.12 μM, respectively), DU-145 cancer cell line (IC50= 11.55 μM, 6.9 μM and 9.54 μM, respectively) and LNCaP cancer cell line (IC50= 11.45 μM and 26.91 μM, respectively). Some compounds were evaluated for their apoptotic caspases protein expression (EGFR/PI3K/AKT pathway) by Western blot analysis in androgen independent- PC3 cells. BAX, caspase 9, caspsase 3 and anti-apoptotic BcL-2 mRNA levels of some compounds were also investigated. In addition, molecular modeling studies of the compounds on MetAP-2 enzyme active site were evaluated in order to get insight into binding mode and energy. Conclusion:: A series of Flurbiprofen-thioether derivatives were synthesized. This study presented that some of the synthesized compounds have remarkable anticancer and apoptotic activities against prostate cancer cells. Also, molecular modeling studies exhibited that there is a correlation between molecular modeling and anticancer activity results.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

scholarly journals CD40 is Positively Correlated with the Expression of Nucleophosmin in Cisplatin-Resistant Bladder Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chenshuo Luo ◽  
Ting Lei ◽  
Man Zhao ◽  
Qian Meng ◽  
Man Zhang
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gene Knockout ◽  
Cancer Cell Lines ◽  
Fold Change ◽  
Bladder Cancer Cell ◽  
Drug Resistant ◽  
Go Analysis ◽  
Differential Proteins

Objective. To verify and evaluate the value of CD40 as a noninvasive biomarker of cisplatin-resistant bladder cancer, we studied the expression of CD40 and the correlation between nucleophosmin (NPM1) and CD40 in cisplatin-resistant bladder cancer. Methods. Three cisplatin-resistant bladder cancer cell lines (T24/0.8DDP, BIU87/0.3DDP, and PUMC-91/0.6DDP) were studied, and lentivirus was used to silence NPM1 expression. The expression of CD40 and NPM1 in three NPM1 silencing bladder cancer cell lines were detected by fluorescence microscopy and Western Blot. The effects and proteomic bioinformatics of NPM1 gene knockout on cisplatin-resistant bladder cancer cells were analyzed by liquid chromatography-mass spectrometry (LC-MS) and gene ontology analysis (GO analysis). Results. The NPM1 gene was successfully silenced in three drug-resistant bladder cancer cell lines by lentivirus infection. The knockdown efficiency was 70%. After NPM1 gene knockout, 492 differential proteins were detected by LC-MS, whose fold change was more than 1.5 p<0.05. A total of 57022 peptides, 54347 unique peptides, and 6686 protein groups were identified in all proteins of the tested cells (FDR < 0.01). Hierarchical clustering and principal component analysis showed that 264 functional proteins were downregulated and 228 functional proteins were upregulated in the gene silencing group compared with those of the negative controls. By GO analysis, the proteins affected by NPM1 cover a large number of proteins with biological functions, which may play an important role in the development of tumor in 492 differential proteins. The CD40 was the most significantly downregulated protein after NPM1 silencing, with a difference of 2.6-fold change in abundance. Conclusions. There is a positive correlation between CD40 protein and NPM1 protein in drug-resistant bladder cancer. Because NPM1 can reflect the characteristics of bladder cancer, CD40 may be a more sensitive marker for monitoring the prognosis of bladder cancer.

Enhanced Efficacy of Gefitinib in Drug‐Sensitive and Drug‐Resistant Cancer Cell Lines after Arming with a Singlet Oxygen Releasing Moiety

ChemMedChem ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. 794-798
Author(s):  
Kunshan Huang ◽  
Beibei Huo ◽  
Dongyao Li ◽  
Jinping Xue ◽  
Juanjuan Chen
Keyword(s):  
Singlet Oxygen ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Drug Resistant

scholarly journals Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics

2015 ◽  
Vol 8 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Stefan Vallo ◽  
Martin Michaelis ◽  
Florian Rothweiler ◽  
Georg Bartsch ◽  
Kilian M. Gust ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Urothelial Cancer ◽  
Cancer Cell Lines ◽  
Drug Resistant ◽  
Second Line ◽  
Urothelial Cancer Cell

Comprehensive Study of Sansalvamide A Derivatives and their Structure–Activity Relationships against Drug-Resistant Colon Cancer Cell Lines

2008 ◽  
Vol 51 (3) ◽  
pp. 530-544 ◽  
Author(s):  
Katerina Otrubova ◽  
Gerald Lushington ◽  
David Vander Velde ◽  
Kathleen L. McGuire ◽  
Shelli R. McAlpine
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Drug Resistant ◽  
Structure Activity ◽  
Colon Cancer Cell Lines ◽  
Sansalvamide A ◽  
Comprehensive Study

scholarly journals Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Radosław Januchowski ◽  
Karolina Sterzyńska ◽  
Katarzyna Zaorska ◽  
Patrycja Sosińska ◽  
Andrzej Klejewski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Ovarian Cancer Cell Lines ◽  
Genes Expression ◽  
Mdr Genes

scholarly journals Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

2016 ◽  
Vol 12 (3) ◽  
pp. 2065-2070 ◽  
Author(s):  
Jin Liu ◽  
Xiaohua Wu ◽  
Hongmei Liu ◽  
Yijuan Liang ◽  
Xinping Gao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Drug Resistant ◽  
Ovarian Cancer Cell Lines
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