Synthesis and Evaluation of Heterocycles Based Chalcone Derivatives as Antiproliferative Agents

2018 ◽  
Vol 18 (7) ◽  
pp. 1044-1053
Author(s):  
Betül Kaya Çavuşoğlu ◽  
Özlem Atlı ◽  
Gözde Görmüş ◽  
Yusuf Özkay ◽  
Zafer Asım Kaplancıklı
Keyword(s):  
Flow Cytometric Analysis ◽  
A549 Cells ◽  
Cytotoxic Agents ◽  
Apoptotic Pathway ◽  
Antiproliferative Agents ◽  
Chalcone Derivatives ◽  
Flow Cytometric ◽  
Elemental Analyses ◽  
Ic50 Values ◽  
Ft Ir

Background: The lack of selectivity and development of drug-resistance encourage researchers to search for novel, more efficient and multi-targeted agents with less toxicity. Objective: In this paper, a series of novel chalcone derivatives bearing diverse heterocycles have been synthesized and evaluated for their antiproliferative activity against A549 (Human Lung Adenocarcinoma) and C6 (Rat Brain Glioma) cells. Method: Structures of the title compounds (3-18) were verified by FT-IR, 1H NMR, 13C NMR, HRMS spectral data and elemental analyses. Antiproliferative activities of the compounds were evaluated using MTT assay, BrdU method, and flow cytometric analysis. Results: Compounds 9 and 15 were revealed as the most promising cytotoxic agents due to their selectivity towards A549 cells with lower IC50 values (IC50=0.05 µM and IC50=0.0316 µM) than cisplatin (IC50=0.06 µM). Flow cytometric analysis of compounds 9 and 15 showed that they affected lung cancer cells by the apoptotic pathway. Conclusion: It is concluded that this study will contribute to the research of novel antiproliferative agents.

scholarly journals Synthesis, Anti-Tumor Activity and Apoptosis-Inducing Effect of Novel Dimeric Keggin-Type Phosphotungstate

2021 ◽  
Vol 11 ◽  
Author(s):  
Yingxue Xue ◽  
Yifei Yin ◽  
He Li ◽  
Mingyu Chi ◽  
Jiaxin Guo ◽  
...  
Keyword(s):  
Flow Cytometric Analysis ◽  
A549 Cells ◽  
Antitumor Action ◽  
Dependent Manner ◽  
Keggin Type ◽  
Flow Cytometric ◽  
Ft Ir ◽  
Octadecyltrimethylammonium Bromide ◽  
Mcf 7

A dimeric Keggin-type phosphotungstate (ODA)10[(PW11FeO39)2O]·9H2O (abbreviated as ODA10[(PW11Fe)2], ODA = octadecyltrimethylammonium bromide) was synthesized and investigated comprehensively its antitumor activity on MCF-7 and A549 cells. The dimeric structure and amorphous morphology were characterized by FT-IR, UV-vis-DRS, SEM and XRD. The in vitro MTT assay of ODA10[(PW11Fe)2] showed anticancer activity on MCF-7 and A549 cells in a dose- and time-dependent manner, and the IC50 values for MCF-7 and A549 cells at 48 h were 5.83 μg/ml and 3.23 μg/ml, respectively. The images of the ODA10[(PW11Fe)2]-treated cells observed by inverted biological microscope exhibited the characteristic morphology of apoptosis. Flow cytometric analysis showed cell apoptosis and cycle arrested at S phase induced by ODA10[(PW11Fe)2]. The above results illuminated the main mechanism of the antitumor action of ODA10[(PW11Fe)2] on MCF-7 and A549 cells, indicating that this dimeric phosphotungstate is a promising anticancer drug.

Dynamic Assessment of Apoptosis for In Vitro Design of Bortezomib Combination Therapies for Lymphoid Malignancies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2494-2494
Author(s):  
Lauren C. Wallis ◽  
Matthew J. Streetly ◽  
Rebecca Auer ◽  
John Gribben ◽  
Dean Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Real Time ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Growth Characteristics ◽  
Cytotoxic Agents ◽  
Alamar Blue ◽  
Apoptosis Induction ◽  
Flow Cytometric ◽  
Induction Of Apoptosis

Abstract Conventional techniques for assessing drug response and apoptosis induction rely on static assessment of cellular changes at predetermined time points (e.g. detection of exposed membrane phospholipids by Annexin V). The Kinetics of Optical Response assay (KOR) is a new technique that detects induction of apoptosis dynamically. It employs a spectrophotometric methodology to detect changes in optical density associated with membrane blebbing related to growth and death, allowing detection of apoptosis in real time. The KOR assay has already predicted the response to cytotoxic agents of AML cell lines and primary samples. This study uses the KOR assay in lymphoid malignancy and shows sensitivity to apoptosis induction by conventional and novel agents including bortezomib. The lymphoma cell line DOHH2 (t(14;18)), U266 (myeloma), K562 (CML) and primary CLL cells were used in this study with HL60 (AML) as a control. Cells were seeded in 96 well plates and treated with a variety of drugs alone or in combination (cytarabine, fludarabine, doxorubicin, daunorubicin, etoposide, melphalan, bortezomib) at multiple concentrations. Measurements were made at 5 min. intervals for up to 48 hrs and analysed using KORSoft™ software to generate apoptotic response curves. To validate this approach conventional techniques were used for comparison (Alamar Blue for cytotoxicity and flow cytometric analysis of cell cycle and apoptosis using propidium iodide and Annexin V staining respectively). The KOR assay can show changes in growth characteristics, induction of apoptosis and necrosis in response to drugs permitting a continuous analysis for maximum sensitivity (Smax). DOHH2 was found to be dose responsive to four of the drugs used, with the Smax for 10μM daunorubicin at 6 hours (48%), 1μM doxorubicin at 8 hours (38%), 100μM etoposide at 8 hours (52%), and minimally to 100μM cytarabine at 16 hours (21%). There was no effect from fludarabine. The addition of bortezomib increased Smax to 89% with etoposide and to a lesser degree with the other cytotoxic drugs. U266 showed a similar spectrum of results with greatest Smax with 100μM melphalan at 9 hours (57%) enhanced to 78% with the addition of bortezomib. There was minimal response to cytarabine and fludarabine. Parallel flow cytometric analysis using Annexin V and PI showed similar results to those from the KOR assay confirming the assessment of apoptosis to be valid. Cell cycle analysis showed an increased sub-G1 peak in keeping with apoptosis at times of Smax assessed by the KOR assay. The Alamar Blue cytotoxicity assay showed a dose dependent decrease in cell proliferation in response to increasing drug dose again paralleling other apoptosis measurements implying an apoptotic effect due to drug action and correlate well with those from the KOR assay. Primary CLL samples following CD19 selection were cultured with and without IL4 and exposed to the KOR assay with cytotoxics and bortezomib. Culture with IL4 alone gave good growth characteristics and revealed the combination of etoposide and bortezomib to provide the best induction of apoptosis (Smax 82%) compared to etoposide (26%) or bortezomib (32%) alone. The KOR assay is a microtitre approach to the assessment in real time of apoptosis. This study suggests the combination of bortezomib and etoposide is effective for lymphoma. Such approaches can accelerate the development of effective clinical trials.

Microwave-Assisted Synthesis of Arene Ruthenium(II) Complex as Apoptosis Inducer of A549 Cells

2013 ◽  
Vol 66 (11) ◽  
pp. 1422 ◽  
Author(s):  
Qiong Wu ◽  
Jian Wu ◽  
Wen-Jie Mei ◽  
Qi Wang ◽  
Zhao Zhang ◽  
...  
Keyword(s):  
Human Lung ◽  
Flow Cytometric Analysis ◽  
A549 Cells ◽  
Microwave Assisted Synthesis ◽  
Dna Molecules ◽  
Microwave Assisted ◽  
Flow Cytometric ◽  
Apoptosis Inducer ◽  
Lung Adenocarcinoma A549 ◽  
Tumour Activity

An arene ruthenium(ii) complex coordinated with 2-(2-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, [(η6-C6H6)Ru(o-ClPIP)Cl]Cl (1), has been prepared by using microwave-assisted synthesis technology. The anti-tumour activity of this complex against various tumour cells has been evaluated by MTT assay and the results show that complex 1 exhibits selective inhibitory activity against the growth of human lung adenocarcinoma A549 cells with IC50 = 31.58 μM. Further studies by flow cytometric analysis showed that apoptosis of A549 cells was observed when dealt with complex 1. Furthermore, complex 1 exhibits excellent binding affinity with DNA molecules which was confirmed by spectroscopy methods, as well viscosity and melting point experiments. As a result, the conformation of DNA molecules was disturbed by complex 1.

scholarly journals Morphological alterations and G0/G1 cell cycle arrest induced by curcumin in human SK-MEL-37 melanoma cells

2010 ◽  
Vol 53 (2) ◽  
pp. 343-352 ◽  
Author(s):  
Marcella Lemos Brettas Carneiro ◽  
Elaine Paulucio Porfírio ◽  
Andréia Hanada Otake ◽  
Roger Chammas ◽  
Sônia Nair Báo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometric Analysis ◽  
Melanoma Cells ◽  
G1 Arrest ◽  
Scanning Electronic Microscopy ◽  
Apoptotic Pathway ◽  
Morphological Alterations ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
G1 Cell Cycle Arrest

The aim of this work was to study the effect of curcumin on cell cycle in the human SK-MEL-37 melanoma cell line. In addition, morphological and structural analyses were also performed. Flow cytometric analysis showed a G0/G1 arrest at 5 µM after 24 h exposure and a concentration-dependent increase in the proportion of sub-G0 hypodiploid cells. Typical apoptotic events were also observed by the fluorescence microscopy, transmission and scanning electronic microscopy. Loss of mitochondrial membrane potential was not detected. Results suggested that curcumin could arrest human melanoma cells at G0/G1 phase and induce a mitochondrial-independent apoptotic pathway.

scholarly journals Flow cytometric detection of erythropoietic cytotoxicity in mouse bone marrow.

1991 ◽  
Vol 39 (1) ◽  
pp. 15-21 ◽  
Author(s):  
V M Benning ◽  
M B Maratrat ◽  
E C Fournier ◽  
C P Melcion ◽  
A C Cordier
Keyword(s):  
Bone Marrow ◽  
Alkylating Agents ◽  
Flow Cytometric Analysis ◽  
Cytotoxic Agents ◽  
Mouse Bone Marrow ◽  
Dna And Rna ◽  
Flow Cytometric ◽  
Polychromatic Erythrocytes ◽  
Kinetics Of ◽  
Dose Dependent

Erythroblast proliferation and maturation in bone marrow are the processes leading to the formation of polychromatic erythrocytes (PE) and normochromatic erythrocytes (NE), respectively. PE contain RNA but no DNA, and can therefore be distinguished both from NE (which lack both RNA and DNA) and from nucleated cells (which contain both DNA and RNA). Cytotoxic agents that induce impairment of the maturation process change the PE:NE ratio. We have developed a simple and rapid method of determining the PE:NE ratio, based on flow cytometric analysis of formaldehyde-fixed, acridine orange (AO)-stained cells. The effects of cyclophosphamide (CP), mitomycin C (MMC), and vincristine (VC) were tested and the PE:NE ratio was evaluated over 7 days of treatment. In this study we monitored the kinetics of these compounds and were able to demonstrate both a time- and a dose-dependent effect. We detected a difference between the effects of the alkylating agents tested and those induced by the spindle inhibitor tested. Flow cytometry of fixed bone marrow samples stained with AO provides more information, better and more rapid statistical analysis, than conventional microscopic methods for counting the PE:NE ratio.

scholarly journals New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity

Marine Drugs ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. 35 ◽  
Author(s):  
Stella Cascioferro ◽  
Alessandro Attanzio ◽  
Veronica Di Sarno ◽  
Simona Musella ◽  
Luisa Tesoriere ◽  
...  
Keyword(s):  
Cell Line ◽  
Flow Cytometric Analysis ◽  
Human Tumor ◽  
Imidazole Ring ◽  
Cycle Arrest ◽  
Morphological Evaluation ◽  
Flow Cytometric ◽  
Ic50 Values ◽  
Hct 116 ◽  
Mcf 7

New analogs of nortopsentin, a natural 2,4-bis(3′-indolyl)imidazole alkaloid, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, and in which a 7-azaindole portion substituted the original indole moiety, were efficiently synthesized. Among all derivatives, prescreened against the HCT-116 colon rectal carcinoma cell line, the two most active compounds were selected and further investigated in different human tumor cells showing IC50 values in the micromolar and submicromolar range. Flow cytometric analysis of propidium iodide-stained MCF-7 cells demonstrated that both the active derivatives caused cell cycle arrest in the G0–G1 phase. The cell death mechanism induced by the compounds was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observed morphological evaluation using acridine orange/ethidium bromide double staining. Moreover, further tested on intestinal normal-like differentiated Caco-2 cell line, they exhibited preferential toxicity towards cancer cells.

scholarly journals Novel Substituted Purine Isosteres: Synthesis, Structure-Activity Relationships and Cytotoxic Activity Evaluation

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 247
Author(s):  
Spyridon Dimitrakis ◽  
Efthymios-Spyridon Gavriil ◽  
Athanasios Pousias ◽  
Nikolaos Lougiakis ◽  
Panagiotis Marakos ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Hct116 Cell ◽  
Human Fibroblasts ◽  
Flow Cytometric Analysis ◽  
Flow Cytometric ◽  
Structure Activity ◽  
M Phase ◽  
Ic50 Values ◽  
Normal Human ◽  
Induced Apoptosis

A number of pyrrolo[2,3-c]pyridines, pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines were designed and synthesized as antiproliferative agents. The target compounds possessed selected substituents in analogous positions on the central scaffold that allowed the extraction of interesting SARs. The cytotoxic activity of the new derivatives was evaluated against prostatic (PC-3) and colon (HCT116) cell lines, and the most potent analogues showed IC50 values in the nM to low µM range, while they were found to be non-toxic against normal human fibroblasts (WI-38). Flow cytometric analysis of DNA content revealed that the most promising derivative 14b caused a statistically significant accumulation of PC-3 cells at G2/M phase and induced apoptosis in PC-3 cells.

scholarly journals C1QTNF6 regulates cell proliferation and apoptosis of NSCLC in vitro and in vivo

2020 ◽  
Author(s):  
Wei Zhang ◽  
Ganzhu Feng
Keyword(s):  
Cell Proliferation ◽  
Cancer Progression ◽  
Colony Formation ◽  
Cell Function ◽  
Flow Cytometric Analysis ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Flow Cytometric

Objectives: Lung cancer has been reported as the leading cause of cancer-associated death in humans, and its incidence continues to increase in the world. A growing number of studies have shown that dysregulated genes are associated with the occurrence and poor prognosis of a variety of tumors, including NSCLC. C1q/tumor necrosis factor-related protein 6 (C1QTNF6), a member of the CTRP family, has been revealed to play a role in carcinogenesis and cancer progression. Nevertheless, the effects and mechanisms of C1QTNF6 in NSCLC remain unrevealed. Materials and methods: MTT and colony formation, flow cytometric and transwell assays were performed to explore the cell function. RT-PCR and western blot were used to analyze the mRNA and protein expression. Results: In this study, we found that C1QTNF6 significantly promoted the proliferation of SPCA1 and A549 cells by MTT and colony formation assays. In addition, downregulation of C1QTNF6 weakened the tumor growth in vivo. Besides, C1QTNF6 remarkably reduced apoptosis by flow cytometric analysis and TUNEL assay. Furthermore, the capability of migration and invasion was obviously enhanced when C1QTNF6 overexpression. Conclusion: Overall, our results demonstrated that inhibition of C1QTNF6 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and in vivo of NSCLC. Based on the above results, our study provided us with a new and key perspective in understanding and treating NSCLC.

scholarly journals Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes.

1995 ◽  
Vol 182 (5) ◽  
pp. 1597-1601 ◽  
Author(s):  
B Verhoven ◽  
R A Schlegel ◽  
P Williamson
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Flow Cytometric Analysis ◽  
Dna Degradation ◽  
Activated Macrophages ◽  
Apoptotic Pathway ◽  
Intracellular Location ◽  
Flow Cytometric ◽  
Lymphocyte Cell

The appearance of phosphatidylserine (PS) on the cell surface during apoptosis in thymocytes and cytotoxic T lymphocyte cell lines provokes PS-dependent recognition by activated macrophages. Flow cytometric analysis of transbilayer lipid movements in T lymphocytes undergoing apoptosis reveals that downregulation of the adenosine triphosphate-dependent amino-phospholipid translocase and activation of a nonspecific lipid scramblase are responsible for PS reaching the surface from its intracellular location. Both mechanisms are expressed at the same time, and precede DNA degradation, zeiosis, and cell lysis in the apoptotic pathway.

scholarly journals Ilimaquinone Induces Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma Cells

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 296 ◽  
Author(s):  
Cheng-Wen Lin ◽  
Li-Yuan Bai ◽  
Jui-Hsin Su ◽  
Chang-Fang Chiu ◽  
Wei-Yu Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Flow Cytometric Analysis ◽  
Reactive Oxygen Species Generation ◽  
Flow Cytometric ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
Anti Tumor Activity

In this study, the anti-tumor activity of ilimaquinone (IQ), a sesquiterpene quinone isolated from marine sponge Halichondria sp., in oral squamous cell carcinoma (OSCC) cells, was investigated. IQ suppressed the viability of the OSCC cell lines SCC4 and SCC2095 with IC50 values of 7.5 and 8.5 μM, respectively. Flow cytometric analysis demonstrated that IQ induced caspase-dependent apoptosis in SCC4 cells and modulated the expression of several cell growth-related gene products, including Akt, p38, Mcl-1, and p53. Notably, p53 knockdown caused higher resistance to IQ’s anti-tumor activity. In addition, IQ increased reactive oxygen species generation, which was partially reversed by the addition of antioxidants. Furthermore, it triggered autophagy, as evidenced by acidic organelle formation and LC3B-II and Atg5 expression in SCC4 cells. Pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine partially decreased IQ-induced apoptosis, suggesting that IQ induced protective autophagy. In summary, IQ has potential to be used in OSCC therapy.

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