A New Pentafluorothio-Substituted Curcuminoid with Superior Antitumor Activity

A new and readily available pentafluorothiophenyl-substituted N-methyl-piperidone curcuminoid 1a was prepared and investigated for its anti-proliferative, pro-apoptotic and cancer stem cell-differentiating activities against a panel of human tumor cell lines derived from various tumor entities. The compound 1a was highly anti-proliferative and reached IC50 values in the nanomolar concentration range. 1a was superior to the known anti-tumorally active curcuminoid EF24 (2) and its known N-ethyl-piperidone analog 1b in all tested tumor cell lines. Furthermore, 1a induced a noticeable increase of intracellular reactive oxygen species in HT-29 colon adenocarcinoma cells, which possibly leads to a distinct increase in sub-G1 cells, as assessed by cell cycle analysis. A considerable activation of the executioner-caspases 3 and 7 as well as nuclei fragmentation, cell rounding, and membrane protrusions suggest the triggering of an apoptotic mechanism. Yet another effect was the re-organization of the actin cytoskeleton shown by the formation of stress fibers and actin aggregation. 1a also caused cell death in the adherently cultured glioblastoma cell lines U251 and Mz54. We furthermore observed that 1a strongly suppressed the stem cell properties of glioma stem-like cell lines including one primary line, highlighting the potential therapeutic relevance of this new compound.

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Bioactivities of essential oils from different parts of Spiranthera odoratissima (Rutaceae)

Rodriguésia ◽

10.1590/2175-7860202071050 ◽

2020 ◽

Vol 71 ◽

Author(s):

Fernando Duarte Cabral ◽

Cassia Cristina Fernandes ◽

Arthur Barcelos Ribeiro ◽

Iara Squarisi Squarisi ◽

Denise Crispim Tavares ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Normal Cell ◽

Human Tumor ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Ic50 Values ◽

Mcf 7

Abstract This paper aims to investigate, for the first time, in vitro antitubercular, antileishmanial and antiproliferative activities of essential oils (EOs) from S. odoratissima leaves and flowers - grown in midwestern Brazil - against Mycobacterium tuberculosis, promastigote forms of Leishmania amazonensis and human tumor cell lines. Antimycobacterial activity of EOs was evaluated in terms of the minimal inhibitory concentration (MIC). EOs from leaves and flowers showed to be active antimicrobials against M. tuberculosis, since MIC values were 150 µg/mL and 162.5 µg/mL, respectively. Both EOs exhibited significant activity against promastigote forms of L. amazonensis; IC50 values (50% growth inhibition) were 14.36 ± 2.02 (EOs from leaves) and 19.89 ± 2.66 µg/mL (EOs from flowers). Antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor (MCF-7, HeLa and M059J) cell lines was performed by the XTT assay; results were expressed as IC50 (50% cell growth inhibition) and the selective index was calculated. IC50 values of EOs from leaves and flowers obtained in normal cell lines for were 502.97 ± 40.33 µg/mL and 370.60 ± 2.01 µg/mL, respectively. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were significantly lower than those obtained in normal cell lines of MCF-7 cells (367.57 ± 4.46 µg/mL-EOs from leaves and 357.70 ± 1.85 µg/mL-EOs from flowers) and M059J cells (492.53 ± 56.67 µg/mL-EOs from leaves and 324.90 ± 6.72 µg/mL-EOs from flowers), thus, indicating selectivity. These in vitro results showed that EOs from S. odoratissima may be an antimycobacterial, antiparasitic and antitumor agent.

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Five New Meroterpenoids from the Fruiting Bodies of the Basidiomycete Clitocybe clavipes with Cytotoxic Activity

Molecules ◽

10.3390/molecules24224015 ◽

2019 ◽

Vol 24 (22) ◽

pp. 4015 ◽

Cited By ~ 3

Author(s):

Zhaocui ◽

Xudong ◽

Hanqiao ◽

Xinyi ◽

Guoxu ◽

...

Keyword(s):

Tumor Cell ◽

Cytotoxic Activity ◽

Cell Lines ◽

Human Tumor ◽

Tumor Cell Lines ◽

Fruiting Bodies ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Ic50 Values

Five new meroterpenoids, clavipols A–B (1–2) with a 12-membered ether ring and clavilactones G–I (3–5) having a 10-membered carbocycle connected to a hydroquinone and an α,β-epoxy/unsaturated lactone, were obtained from the fruiting bodies of the basidiomycete Clitocybe clavipes. Their structures were determined by comprehensive analysis of their spectroscopic data, and the absolute configuration of 1 was established by quantum chemical calculations of electronic circular dichroism (ECD). All the isolated compounds (1–5) were tested for their cytotoxic activity against three human tumor cell lines (Hela, SGC-7901, and SHG-44) in vitro after treatment for 48 h. Compound 4 exhibited moderate cytotoxic activity against Hela and SGC-7901 tumor cell lines, with IC50 values of 23.5 and 14.5 µM, respectively.

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Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms

Molecules ◽

10.3390/molecules25040859 ◽

2020 ◽

Vol 25 (4) ◽

pp. 859 ◽

Cited By ~ 1

Author(s):

Alessandro Attanzio ◽

Simone D’Agostino ◽

Rosalia Busà ◽

Anna Frazzitta ◽

Simona Rubino ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Human Tumor ◽

Cycle Phase ◽

Tumor Cell Lines ◽

M Cell ◽

Cell Progression ◽

Ligand Interactions ◽

Ic50 Values ◽

Hct 116

In this study cytotoxicity of organotin(IV) compounds with 1,2,4-triazolo[1,5-a]pyrimidines, Me3Sn(5tpO) (1), n-Bu3Sn(5tpO) (2), Me3Sn(mtpO) (3), n-Bu3Sn(mtpO) (4), n-Bu3Sn(HtpO2) (5), Ph3Sn(HtpO2) (6) where 5HtpO = 4,5-dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, HmtpO = 4,7-dihydro-5-methyl-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, and H2tpO2 = 4,5,6,7-tetrahydro-5,7- dioxo-[1,2,4]triazolo-[1,5-a]-pyrimidine, was assessed on three different human tumor cell lines: HCT-116 (colorectal carcinoma), HepG2 (hepatocarcinoma) and MCF-7 (breast cancer). While 1 and 3 were inactive, compounds 2, 4, 5 and 6 inhibited the growth of the three tumor cell lines with IC50 values in the submicromolar range and showed high selectivity indexes towards the tumor cells (SI > 90). The mechanism of cell death triggered by the organotin(IV) derivatives, investigated on HCT-116 cells, was apoptotic, as evident from the externalization of phosphatidylserine to the cell surface, and occurred via the intrinsic pathway with fall of mitochondrial inner membrane potential and production of reactive oxygen species. While compound 6 arrested the cell progression in the G2/M cell cycle phase and increased p53 and p21 levels, compounds 2, 4 and 5 blocked cell duplication in the G1 phase without affecting the expression of either of the two tumor suppressor proteins. Compounds 1 and 2 were also investigated using single crystal X-ray diffraction and found to be, in both cases, coordination polymers forming 1 D chains based on metal-ligand interactions. Interestingly, for n-Bu3Sn(5tpO)(2) H-bonding interactions between 5tpO− ligands belonging to adjacent chains were also detected that resemble the “base-pairing” assembly and could be responsible for the higher biological activity compared to compound 1. In addition, they are the first example of bidentate N(3), O coordination for the 5HtpO ligand on two adjacent metal atoms.

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Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665296 ◽

1983 ◽

Vol 50 (03) ◽

pp. 726-730 ◽

Cited By ~ 11

Author(s):

Hamid Al-Mondhiry ◽

Virginia McGarvey ◽

Kim Leitzel

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Cell Lines ◽

Human Tumor ◽

Human Platelets ◽

Factor Vii ◽

Coagulation System ◽

Breast Adenocarcinoma ◽

Activate Factor ◽

Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

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Differential Increases in Glutathione S-Transferase Activities in a Range of Multidrug-Resistant Human Tumor Cell Lines

Cancer Communications ◽

10.3727/095535489820875057 ◽

1989 ◽

Vol 1 (6) ◽

pp. 359-365 ◽

Cited By ~ 36

Author(s):

Richard D. H. Whelan ◽

Louise K. Hosking ◽

Alan J. Townsend ◽

Kenneth H. Cowan ◽

Bridget T. Hill

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Human Tumor ◽

Multidrug Resistant ◽

Tumor Cell Lines ◽

Glutathione S Transferase ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

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Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190730164952 ◽

2020 ◽

Vol 17 (4) ◽

pp. 512-517

Author(s):

Ognyan Ivanov Petrov ◽

Yordanka Borisova Ivanova ◽

Mariana Stefanova Gerova ◽

Georgi Tsvetanov Momekov

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Biological Activities ◽

Human Tumor ◽

Mannich Bases ◽

In Vitro Cytotoxicity ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

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Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

RSC Advances ◽

10.1039/d1ra03509f ◽

2021 ◽

Vol 11 (38) ◽

pp. 23310-23329

Author(s):

Viviana Cuartas ◽

Alberto Aragón-Muriel ◽

Yamil Liscano ◽

Dorian Polo-Cerón ◽

Maria del Pilar Crespo-Ortiz ◽

...

Keyword(s):

Molecular Docking ◽

Dna Binding ◽

Tumor Cell ◽

Anticancer Activity ◽

Cell Lines ◽

Human Tumor ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

A new series of quinazoline-based chalcones and pyrimidodiazepines were tested against 60 human tumor cell lines.

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Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽

10.3390/biomedicines9010092 ◽

2021 ◽

Vol 9 (1) ◽

pp. 92

Author(s):

Bashir Lawal ◽

Yen-Lin Liu ◽

Ntlotlang Mokgautsi ◽

Harshita Khedkar ◽

Maryam Rachmawati Sumitra ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Cancer Cell ◽

Human Tumor ◽

Cancer Cell Lines ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

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