Synthesis of New Calixarene Derivatives and Evaluation of Their Cytotoxic Activity

2021 ◽  
Author(s):  
Mehmet Oguz ◽  
Ayse Yildirim ◽  
Irem Mukaddes Durmus ◽  
Serdar Karakurt ◽  
Mustafa Yilmaz
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Carcinoma Cells ◽  
Spectroscopic Techniques ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
H Nmr ◽  
Cancerous Cells ◽  
Dose Dependent ◽  
Derivatives Of

Abstract Since calixarenes are more easily synthesized and functionalized than other supramolecules, they are compounds of interest in organic chemistry. In this study, the dihydrazide (3a and 3b) and diamino propyl (6a and 6b) derivatives of p-tert-butylcalix[4]arene and calix[4]arene were synthesized. Then the L-proline methyl ester substituted chlorocyclopropenium was reacted with the calix[4]arene derivatives (3a, 3b, 6a, and 6b) at room temperature in CH2Cl2 to obtain calix[4]arene superbase derivatives (4a, 4b, 7a, and 7b) in 75%, 60%, 70% and 55% yield, respectively. The synthesized compounds' structure was elucidated by using spectroscopic techniques (FTIR, 1H NMR, and 13C NMR ). The cytotoxic properties of the calix[4]arene superbase derivatives were investigated against different human cancerous cells, including A549, DLD-1, HEPG2, and PC-3, as well as human healthy epithelium cell line PNT1A. The cytotoxicity results showed that calix[4]arene superbase derivatives inhibited the proliferation of DLD-1, A549, HEPG2, and PC-3 cells in a dose-dependent manner. Compound 7a had the highest toxic effect on colorectal carcinoma (IC50: 4.7 µM), and the IC50 values were 18.5 µM and 74.4µM against human prostate and lung cancer cells, respectively. Furthermore, the compound 4b was found more effective on hepatocellular carcinoma cells (IC50: 210.2 µM). As a result, the synthesized calix[4]arene superbase derivatives can be developed to treat different human cancer cells. They can be considered as a preliminary result for molecular-level research.

scholarly journals Effect of Calomelanone, a Dihydrochalcone Analogue, on Human Cancer Apoptosis/Regulated Cell Death in an In Vitro Model

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Wasitta Rachakhom ◽  
Ratana Banjerdpongchai
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Regulated Cell Death

Calomelanone, 2 ′ ,6 ′ -dihydroxy-4,4 ′ -dimethoxydihydrochalcone, possesses anticancer activities. This study was conducted to investigate the cytotoxic effect of calomelanone, a dihydrochalcone analogue, on human cancer cells and its associated mechanisms. The cytotoxic effect of calomelanone was measured by MTT assay. Annexin V-FITC/propidium iodide and DiOC6 staining that employed flow cytometry were used to determine the mode of cell death and reduction of mitochondrial transmembrane potential (MTP), respectively. Caspase activities were measured using specific substrates and colorimetric analysis. The expression levels of Bcl-2 family proteins were determined by immunoblotting. Reactive oxygen species were also measured using 2 ′ ,7 ′ -dihydrodichlorofluorescein diacetate and dihydroethidium (fluorescence dyes). Calomelanone was found to be toxic towards various human cancer cells, including acute promyelocytic HL-60 and monocytic leukemic U937 cells, in a dose-dependent manner at 24 h and human hepatocellular HepG2 cells at 48 h. However, the proliferation of HepG2 cells increased at 24 h. Calomelanone was found to induce apoptosis in HL-60 and U937 at 24 h and HepG2 apoptosis at 48 h via the intrinsic pathway by inducing MTP disruption. This compound also induced caspase-3, caspase-8, and caspase-9 activities. Calomelanone upregulated proapoptotic Bax and Bak and downregulated antiapoptotic Bcl-xL proteins in HepG2 cells. Moreover, signaling was also associated with oxidative stress in HepG2 cells. Calomelanone induced autophagy at 24 h of treatment, which was evidenced by staining with monodansylcadaverine (MDC) to represent autophagic flux. This was associated with a decrease of Akt (survival pathway) and an upregulation of Atg5 (the marker of autophagy). Thus, calomelanone induced apoptosis/regulated cell death in HL-60, U937, and HepG2 cells. However, it also induced autophagy in HepG2 depending on duration, dose, and type of cells. Thus, calomelanone could be used as a potential anticancer agent for cancer treatment. Nevertheless, acute and chronic toxicity should be further investigated in animals before conducting investigations in human patients.

Water soluble derivatives of platinum carbonyl Chini clusters: synthesis, molecular structures and cytotoxicity of [Pt12(CO)20(PTA)4]2− and [Pt15(CO)25(PTA)5]2−

2018 ◽  
Vol 47 (13) ◽  
pp. 4467-4477 ◽  
Author(s):  
Lucinda K. Batchelor ◽  
Beatrice Berti ◽  
Cristiana Cesari ◽  
Iacopo Ciabatti ◽  
Paul J. Dyson ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Molecular Structures ◽  
Water Soluble ◽  
Human Cancer Cells ◽  
Derivatives Of

The cytotoxicity towards human cancer cells of water soluble Chini clusters is reported.

scholarly journals Momordica charantiaExtract Induces Apoptosis in Human Cancer Cells through Caspase- and Mitochondria-Dependent Pathways

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Chia-Jung Li ◽  
Shih-Fang Tsang ◽  
Chun-Hao Tsai ◽  
Hsin-Yi Tsai ◽  
Jong-Ho Chyuan ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Dna Fragmentation ◽  
Human Cancer ◽  
Momordica Charantia ◽  
Carcinoma Cells ◽  
Human Cancer Cells ◽  
Adenocarcinoma Cells ◽  
Anti Cancer

Plants are an invaluable source of potential new anti-cancer drugs.Momordica charantiais one of these plants with both edible and medical value and reported to exhibit anticancer activity. To explore the potential effectiveness ofMomordica charantia, methanol extract ofMomordica charantia(MCME) was used to evaluate the cytotoxic activity on four human cancer cell lines, Hone-1 nasopharyngeal carcinoma cells, AGS gastric adenocarcinoma cells, HCT-116 colorectal carcinoma cells, and CL1-0 lung adenocarcinoma cells, in this study. MCME showed cytotoxic activity towards all cancer cells tested, with the approximate IC50ranging from 0.25 to 0.35 mg/mL at 24 h. MCME induced cell death was found to be time-dependent in these cells. Apoptosis was demonstrated by DAPI staining and DNA fragmentation analysis using agarose gel electrophoresis. MCME activated caspase-3 and enhanced the cleavage of downstream DFF45 and PARP, subsequently leading to DNA fragmentation and nuclear condensation. The apoptogenic protein, Bax, was increased, whereas Bcl-2 was decreased after treating for 24 h in all cancer cells, indicating the involvement of mitochondrial pathway in MCME-induced cell death. These findings indicate that MCME has cytotoxic effects on human cancer cells and exhibits promising anti-cancer activity by triggering apoptosis through the regulation of caspases and mitochondria.

scholarly journals L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1542 ◽  
Author(s):  
Agustina DR Nurcahyanti ◽  
Michael Wink
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Carcinoma Cells ◽  
Mass Action ◽  
Combination Method ◽  
Protein Amino Acid ◽  
Human Cancer Cells ◽  
Dna Targeting ◽  
Argininosuccinate Synthase ◽  
Mass Action Law

The non-protein amino acid L-canavanine (L-CAV), an antimetabolite of L-arginine (L-ARG), can alter the 3D conformation of proteins when incorporated into a protein instead of L-ARG. L-CAV inhibits the proliferation of some tumour cells. The deprivation of L-ARG in the culture medium enhances the response of cells to L-CAV. This study aimed to investigate the interaction of L-CAV in combination with the chemotherapeutic drugs, doxorubicin (DOX) or cisplatin (CIS), in cancer cells, especially in the absence of L-ARG. A combination method based on the median-effect principle and mass-action law was used. The following cancer cells were employed: HeLa and Caco-2 cells, overexpressing argininosuccinate synthase (ASS), pancreatic cells (MIA PaCa-2 and BxPC-3) and hepatocellular carcinoma cells (Hep G2 and SK-HEP-1), with down-regulated ASS. When constant and non-constant ratios of L-CAV were combined with DOX and CIS, a synergistic potentiation of cytotoxicity was recorded. Cells expressing high levels of ASS were more sensitive to the treatment as compared to the cells with reduced ASS levels. Overall, this study may provide a new approach to targeting some cancer cells with L-CAV in combination with DNA-targeting drugs such as DOX and CIS, especially those cells which overexpress ASS, such as human cervical and colorectal carcinoma cells.

scholarly journals Hydrodynamic shear-based purification of cancer cells with enhanced tumorigenic potential

2020 ◽  
Vol 12 (1) ◽  
pp. 1-11
Author(s):  
Efraín A Cermeño ◽  
Meghan J O’Melia ◽  
Woojin M Han ◽  
Austin Veith ◽  
Graham Barber ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Adhesion Strength ◽  
Human Cancer ◽  
Low Frequency ◽  
Label Free ◽  
Tumor Initiating Cells ◽  
Adhesive Properties ◽  
Human Cancer Cells ◽  
Tumorigenic Potential ◽  
Cancerous Cells

Abstract Tumor-initiating cells (TICs), a subpopulation of cancerous cells with high tumorigenic potential and stem-cell-like properties, drive tumor progression and are resistant to conventional therapies. Identification and isolation of TICs are limited by their low frequency and lack of robust markers. Here, we characterize the heterogeneous adhesive properties of a panel of human and murine cancer cells and demonstrate differences in adhesion strength among cells, which exhibit TIC properties and those that do not. These differences in adhesion strength were exploited to rapidly (~10 min) and efficiently isolate cancerous cells with increased tumorigenic potential in a label-free manner by use of a microfluidic technology. Isolated murine and human cancer cells gave rise to larger tumors with increased growth rate and higher frequency in both immunocompetent and immunocompromised mice, respectively. This rapid and label-free TIC isolation technology has the potential to be a valuable tool for facilitating research into TIC biology and the development of more efficient diagnostics and cancer therapies.

scholarly journals Identification and Characterization of the Caspase-Mediated Apoptotic Activity of Teucrium mascatense and an Isolated Compound in Human Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 977 ◽  
Author(s):  
Neena Panicker ◽  
Sameera Balhamar ◽  
Shaima Akhlaq ◽  
Mohammed Qureshi ◽  
Tania Rizvi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Annexin V ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
Cell Death Pathways ◽  
Proliferative Effect ◽  
Mcf 7

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of T. mascatense, but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells.

Synthesis, Molecular Characterization, and Biological Activity of Novel Synthetic Derivatives of Chromen-4-one in Human Cancer Cells

2006 ◽  
Vol 49 (13) ◽  
pp. 3800-3808 ◽  
Author(s):  
Vivek Barve ◽  
Fakhara Ahmed ◽  
Shreelekha Adsule ◽  
Sanjeev Banerjee ◽  
Sudhir Kulkarni ◽  
...  
Keyword(s):  
Biological Activity ◽  
Cancer Cells ◽  
Molecular Characterization ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Synthetic Derivatives ◽  
Derivatives Of

Synthesis and cytotoxic activity on human cancer cells of carbamate derivatives of 4β-(1,2,3-triazol-1-yl)podophyllotoxin

2013 ◽  
Vol 64 ◽  
pp. 621-628 ◽  
Author(s):  
Jian-Fei Liu ◽  
Chun-Yan Sang ◽  
Xiao-Hui Xu ◽  
Lin-Lin Zhang ◽  
Xuan Yang ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Derivatives Of

Synthesis, Characterization and Cytotoxic Effect of Some New Thiazolyl Hydrazone Derivatives of 1-Indanone

2021 ◽  
Vol 43 (2) ◽  
pp. 244-244
Author(s):  
Urooj Nazim Urooj Nazim ◽  
Silpa Narayanan Silpa Narayanan ◽  
Mohsin Ali Mohsin Ali ◽  
Khalid Mohammed Khan Khalid Mohammed Khan ◽  
Basharat Ali Basharat Ali ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Cancer ◽  
Human Colon ◽  
Human Leukemia ◽  
Spectroscopic Techniques ◽  
Human Colon Cancer ◽  
Human Cancer Cells ◽  
Anti Cancer ◽  
Derivatives Of ◽  
Cancer Activity

In the present study, a series of twelve thiazolyl hydrazone derivatives of 1-indanone was synthesized and characterized by various spectroscopic techniques such as UV-Visible, NMR, IR and Mass Spectrometry. All the synthesized target compounds were subjected to MTT assay for cytotoxicity screening and evaluation of their anti-cancer activity on various cell lines of human cancer including glioblastoma (SNB-19), prostate cancer (PC-3), Lung cancer (NCI-H460), human ovarian carcinoma (SK-OV-3 and IGROV-1), human leukemia (K-562) and human colon cancer(HCT116).Three synthesized compounds showed promising anti-cancer activity against the colon cancer cell HCT 116 cells with IC50 ranging from 1.25and#177;0.02 to 5.04and#177;0.2 and#181;M. On the other hand all the compounds didn’t show cytotoxic activity against other forms of human cancer cells.

scholarly journals Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33

2012 ◽  
Vol 209 (4) ◽  
pp. 697-711 ◽  
Author(s):  
Ninel Azoitei ◽  
Christopher M. Hoffmann ◽  
Jana M. Ellegast ◽  
Claudia R. Ball ◽  
Kerstin Obermayer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Human Colon ◽  
Dependent Manner ◽  
Tumor Initiating Cells ◽  
Hsp90 Inhibitors ◽  
Hsp90 Inhibition ◽  
Human Cancer Cells

Previous efforts to develop drugs that directly inhibit the activity of mutant KRAS, the most commonly mutated human oncogene, have not been successful. Cancer cells driven by mutant KRAS require expression of the serine/threonine kinase STK33 for their viability and proliferation, identifying STK33 as a context-dependent therapeutic target. However, specific strategies for interfering with the critical functions of STK33 are not yet available. Here, using a mass spectrometry-based screen for STK33 protein interaction partners, we report that the HSP90/CDC37 chaperone complex binds to and stabilizes STK33 in human cancer cells. Pharmacologic inhibition of HSP90, using structurally divergent small molecules currently in clinical development, induced proteasome-mediated degradation of STK33 in human cancer cells of various tissue origin in vitro and in vivo, and triggered apoptosis preferentially in KRAS mutant cells in an STK33-dependent manner. Furthermore, HSP90 inhibitor treatment impaired sphere formation and viability of primary human colon tumor-initiating cells harboring mutant KRAS. These findings provide mechanistic insight into the activity of HSP90 inhibitors in KRAS mutant cancer cells, indicate that the enhanced requirement for STK33 can be exploited to target mutant KRAS-driven tumors, and identify STK33 depletion through HSP90 inhibition as a biomarker-guided therapeutic strategy with immediate translational potential.

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