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 Antiproliferative Activity, Proapoptotic Effect, and Cell Cycle Arrest in Human Cancer Cells of Some Marine Natural Product Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Hong Cui ◽  
Mansour A. E. Bashar ◽  
Islam Rady ◽  
Hussein A. El-Naggar ◽  
Lamiaa M. Abd El-Maoula ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
Hepg2 Cell Line ◽  
Cycle Arrest ◽  
Ic50 Values ◽  
Hct 116 ◽  
Mcf 7

Bioactive constituents of numerous marine organisms have been investigated recently for their preclinical and clinical anticancer activity. Three marine organisms: black-spotted sea cucumber: Pearsonothuria graeffei (Pg), lollyfish: Holothuria atra (Ha), and sea hare: Aplysia dactylomela (Ad), were collected during winter 2019 from Gulf of Aqaba, Red Sea, Egypt, and macerated with ethanol into three different extracts: PgE, HaE, and AdE, where each was in vitro assessed for its antiproliferative and proapoptotic properties on HepG2, HCT-116, and MCF-7 cancer cells. PgE dose-dependently inhibited the growth of HepG2, HCT-116, and MCF-7 cells within IC50 values 16.22, 13.34, and 18.09 μg/mL, respectively, while the IC50 values for the antiproliferative activity of HaE were 12.48, 10.45, and 10.36 μg/mL, respectively, and the IC50 values of AdE were 6.51, 5.33, and 6.87 μg/mL, respectively. All extracts were found to induce G0/G1 cell cycle arrest for HepG2 cells side by side with their inhibition of CDK2 on all three cell lines while all extracts were also showed to induce apoptosis in HepG2 cell line at pre-G1 phase supplemented by their anticancer activity via proapoptotic protein Bax, caspase-3, and cleavage PARP increase, and antiapoptotic protein Bcl-2 downturn. Moreover, necrosis has been relatively noticed in HepG2 cell line as an additional anticancer activity for each extract. Our data introduced three ethanolic marine extracts as natural chemotherapeutic agents to be further developed for cancer control.

Multiparametric flow cytometric analysis in a breast cancer cell line (MCF-7)

2002 ◽  
Vol 28 (3) ◽  
pp. 141-148 ◽  
Author(s):  
Gui Se Ra Lee ◽  
Ki Sung Ryu ◽  
Jong Gu Rha ◽  
Soo Pyung Kim ◽  
Sung Eun Namkoong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Flow Cytometric Analysis ◽  
Cancer Cell Line ◽  
Flow Cytometric ◽  
Mcf 7

scholarly journals An Efficient Synthetic Approach Towards Benzo[b]pyrano[2,3-e][1,4]diazepines, and Their Cytotoxic Activity

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2051
Author(s):  
Islam H. El Azab ◽  
Nadia A.A. Elkanzi
Keyword(s):  
Human Tumor ◽  
Breast Adenocarcinoma ◽  
Cytotoxic Activities ◽  
Synthetic Approach ◽  
Standard Drug ◽  
In Vitro Investigation ◽  
Ic50 Values ◽  
Hct 116 ◽  
Mcf 7

In search of unprecedented tri and/or tetrapod pharmacophoric conjugates, a series of 32 new 4-ethyl-1H-benzo[b][1,4]diazepin-2(3H)-ones were synthesized and properly elucidated using MS, IR, NMR, and elemental analysis. In vitro investigation of 11 compounds of this series, using a panel of two human tumor cell lines namely; human breast adenocarcinoma (MCF-7), and human colorectal carcinoma (HCT-116), revealed promising cytotoxic activities. Among all synthesized compounds, analogue 9 displayed maximum cytotoxicity with IC50 values of 16.19 ± 1.35 and 17.16 ± 1.54 μM against HCT-116 and MCF-7, respectively, compared to standard drug doxorubicin.

Activation of Intrinsic Apoptosis and G1 Cell Cycle Arrest by a Triazole Precursor, N-(4-chlorophenyl)-2-(4-(3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide in Breast Cancer Cell Line

2020 ◽  
Vol 20 (9) ◽  
pp. 1072-1086
Author(s):  
Stephanie B. Arulnathan ◽  
Kok H. Leong ◽  
Azhar Ariffin ◽  
Huda S. Kareem ◽  
Kevin K.H. Cheah
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Line ◽  
Cycle Arrest ◽  
Flow Cytometric ◽  
Mcf 7

Background: Oxadiazoles, triazoles, and their respective precursors have been shown to exhibit various pharmacological properties, namely antitumour activities. Cytotoxic activity was reported for these compounds in various cancer cell lines. Aim and Objectives: In this study, we aim at investigating the mechanism of apoptosis by N-(4-chlorophenyl)-2-(4- (3,4,5-trimethoxybenzyloxy)benzoyl)-hydrazinecarbothioamide, a triazole precursor, henceforth termed compound P7a, in breast cancer cell line, MCF-7. We first screen a series of analogues containing (3,4,5-trimethoxybenzyloxy) phenyl moiety in breast cancer cell lines (MCF-7 and MDA-MB-231) to select the most cytotoxic compound and demonstrate a dose- and time-dependent cytotoxicity. Then, we unravel the mechanism of apoptosis of P7a in MCF-7 as well as its ability to cause cell cycle arrest. Methods: Synthesis was performed as previously described by Kareem and co-workers. Cytotoxicity of analogues containing (3,4,5-trimethoxybenzyloxy)phenyl moiety against MCF-7 and MDA-MB-231 cell lines was evaluated using the MTS assay. Flow cytometric analyses was done using Annexin V/PI staining, JC-1 staining and ROS assay. The activity of caspases using a chemoluminescence assay and western blot analysis was conducted to study the apoptotic pathway induced by the compound in MCF-7 cells. Lastly, cell cycle analysis was conducted using flow cytometry. Results: Upon 48 hours of treatment, compound P7a inhibited the proliferation of human breast cancer cells with IC50 values of 178.92 ± 12.51μM and 33.75 ± 1.20μM for MDA-MB-231 and MCF-7, respectively. Additionally, compound P7a showed selectivity towards the cancer cell line, MCF-7 compared to the normal breast cell line, hTERT-HME1, an advantage against current anticancer drugs (tamoxifen and vinblastine). Flow cytometric analyses using different assays indicated that compound P7a significantly increased the proportion of apoptotic cells, increased mitochondria membrane permeabilisation and caused generation of ROS in MCF-7. In addition, cell cycle analysis showed that cell proliferation was arrested at the G1 phase in the MCF-7 cell line. Furthermore, upon treatment, the MCF-7 cell line showed increased activity of caspase-3/7, and caspase-9. Lastly, the western blot analysis showed the up-regulation of pro-apoptotic proteins along with up-regulation of caspase-7 and caspase-9, indicating that an intrinsic pathway of apoptosis was induced. Conclusion: The results suggest that compound P7a could be a potential chemotherapeutic agent for breast cancer.

scholarly journals A New CDK2 Inhibitor with 3-Hydrazonoindolin-2-One Scaffold Endowed with Anti-Breast Cancer Activity: Design, Synthesis, Biological Evaluation, and In Silico Insights

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 412
Author(s):  
Mohammad M. Al-Sanea ◽  
Ahmad J. Obaidullah ◽  
Mohamed E. Shaker ◽  
Garri Chilingaryan ◽  
Mohammed M. Alanazi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Inhibitory Activity ◽  
Flow Cytometric Analysis ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Intrinsic Activity ◽  
Binding Interaction ◽  
Mcf 7

Background: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. Methods: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. Results: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of HI 5 was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides, HI 5 blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (syn and anti) is responsible for binding affinity and intrinsic activity of HI 5. However, the molecular dynamic studies have confirmed that the syn-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity. Discussion: These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.

scholarly journals Labdane and Abietane Diterpenoids from Juniperus oblonga and Their Cytotoxic Activity

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1561 ◽  
Author(s):  
Qiao ◽  
Khutsishvili ◽  
Alizade ◽  
Atha ◽  
Borris
Keyword(s):  
Cell Lines ◽  
Human Tumor ◽  
2D Nmr ◽  
Human Tumor Cell Lines ◽  
Abietane Diterpenoids ◽  
Whole Plant ◽  
Phytochemical Investigation ◽  
Ic50 Values ◽  
First Time ◽  
Mcf 7

A phytochemical investigation of the whole plant of Juniperus oblonga led to the isolationof one previously undescribed labdane diterpenoid, (4R,5S,9S,10R)‐13‐des‐ethyl‐13‐oxolabda‐8(17),11E‐dien‐19‐oic acid (1), together with nine known diterpenoids (2–3, 6–12), two lignans (4, 5),and a coumarin (13). The structures of all the compounds were elucidated on the basis ofspectrometric data, primarily one‐dimensional (1D)‐ and two‐dimensional (2D)‐NMR and massspectrometry. Electronic circular dichroism (ECD) calculations determined the absoluteconfiguration of 1. In addition, the isolated compounds were evaluated for their cytotoxic activityagainst three human tumor cell lines (HepG2, MCF‐7, and HeLa). 6,12‐Dihydroxyabieta‐5,8,11,13‐tetraen‐7‐one (6) showed moderate cytotoxicity against all three cell lines with IC50 values rangingfrom 24.41 μM to 58.39 μM and trilobinone (10) showed weaker activity with IC50 values rangingfrom 56.93 μM to 79.98 μM. None of the isolated diterpenoids have been previously reported fromJuniperus oblonga, and five compounds are here reported from the genus Juniperus for the first time.

scholarly journals A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

2021 ◽  
Vol 11 (19) ◽  
pp. 9139
Author(s):  
Maria Stefania Sinicropi ◽  
Cinzia Tavani ◽  
Camillo Rosano ◽  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Breast Cancer Cell Lines ◽  
Cellular Functions ◽  
Anticancer Properties ◽  
Cycle Arrest ◽  
In Silico Studies ◽  
Ic50 Values ◽  
Mcf 7

Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.

IN-SILICO AND IN VITRO ASSESSMENT OF SYNTHESIZED DIAZENYLSULFONAMIDES AS APOPTOSIS INDUCERS AND RADICAL SCAVENGERS

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (06) ◽  
pp. 49-59
Author(s):  
Priyambada Kshiroda Nandini Sarangi ◽  
Jyotirmaya Sahoo ◽  
Chita Ranjan Sahoo ◽  
Sudhir Kumar Paidesetty ◽  
Guru Prasad Mohanta
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Radical Scavenging ◽  
Cancer Cell Line ◽  
Scavenging Effect ◽  
Ic50 Values ◽  
Radical Scavenging Effect ◽  
The Individual ◽  
Mcf 7

A series of eight quinoline-thiazole hybrid-bearing diazenylsulfonamides, 4a-4h, were synthesized and characterized by UV-Vis, FT/IR, 1H NMR and lC-MS. These compounds were formed when two prepared intermediate precursors of Schiff-base compounds, (E)-N-((2-chloroquinolin-3-yl)methylene)-4phenylthiazol-2-amine (3a) and (E)-N-((2-chloroquinolin-3-yl)methylene)-4-chlorophenylthiazol-2-amine (3b) were converted to the corresponding diazenyl compounds 4a-4h by treating and coupling with the individual diazonium salts of sulfa-drugs. The results of in vitro cytotoxic activity of the synthesized compounds in two cancer cell lines MCF 7 (human breast cancer cell line) and K562 (myelogenousleukemia cell line) have shown the IC50 values as given: 4b against MCF 7 19.52 and against K562 20.55µM; 4d against MCF 7 15.96 and against K562 13.05µM. Moreover, the compound 4-(((Z)-(2-chloroquinolin-3yl)(4-phenylthiazol-2-ylimino)methyl)diazenyl)benzenesulfonic acid (4d) induced maximum percentage of apoptosis. Furthermore, the in vitro antioxidant activity study revealed that among all the synthesized compounds, compound 4d has an excellent radical scavenging effect. Molecular docking was additionally performed to investigate the binding affinity of H-bonding interaction of synthesized compounds with a targeted enzyme and to compare it with the anticancer drugs, dasatinib, bosutinib and dacarbazine.

PHYTOCHEMICALS ANALYSIS AND CELL CYCLE ARREST ACTIVITY OF ETHANOL EXTRACT OF Litsea cubeba Lour. FRUITS TOWARDS MCF-7/HER-2 CELL LINE

2021 ◽  
Vol 14 (01) ◽  
pp. 16-18
Author(s):  
Aminah Dalimunthe ◽  
Poppy Anjelisa Zaitun Hasibuan ◽  
Muflihah Fujiko ◽  
Masfria ◽  
Denny Satria
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Ethanol Extract ◽  
Litsea Cubeba ◽  
Cycle Arrest ◽  
Her 2 ◽  
Arrest Activity ◽  
Mcf 7

289. Comparison of lymphocyte subsets and function in the rat and mouse testis

2005 ◽  
Vol 17 (9) ◽  
pp. 122 ◽  
Author(s):  
D. Aridi ◽  
D. Pellicci ◽  
P. Hutchinson ◽  
M. P. Hedger
Keyword(s):  
T Cells ◽  
Cell Line ◽  
Tumour Cell ◽  
Flow Cytometric Analysis ◽  
Nkt Cells ◽  
Mouse Testis ◽  
Tumour Cell Line ◽  
Rat Testis ◽  
Flow Cytometric ◽  
Rats And Mice

Testicular leukocytes are assumed to be involved in immunological surveillance against infection and tumours as well as regulation of local immune responses. They are implicated in mechanisms that make the testis a successful site for tissue transplantation in both rats and mice. Our previous studies using multi-colour fluorescence flow cytometric analysis to examine isolated testicular leukocytes in the rat testis have established the existence of a significant population of predominantly CD8+ T cells and a comparable number of lymphocytes expressing natural killer (NK) cell markers (NK and NKT cells). The functional activity of these testicular NK and NKT cells subsequently has been confirmed by a standard flow cytometric cytotoxicity assay using an NK-sensitive tumour cell line (YAC-1) and an NKT-sensitive tumour cell line (U937). Similar analyses of mouse testicular leukocytes have shown a slightly different pattern. The data indicate that mouse testicular lymphocytes comprise T cells, NK cells, and NKT cells, similar to the rat testis. However, while the apparent numerical densities of T cells in rat and mouse testes were similar, the numbers of NK and NKT cells were considerably lower in the mouse. Mouse testicular NKT cells were positive for staining with the tetramer CD1d/αGC, which is used to identify classical NKT cells, whereas rat NKT cells did not stain for this marker. Moreover, the CD8/CD4 T cell ratio in the mouse testis displayed a skewing towards the CD4+ subset. These data highlight the possibility that the immunological environment, and hence the course of immunological events, might be quite different in the testes of the two species. The reasons for these differences are not clear, however they should be taken into account when considering studies of testicular immune processes. Finally, comparative studies of immunological process in the testes of rats and mice may be very informative.

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