Synthesis and biological evaluation of bivalent β-carbolines as potential anticancer agents

MedChemComm ◽  
2016 ◽  
Vol 7 (4) ◽  
pp. 636-645 ◽  
Author(s):  
Hongtao Du ◽  
Hongling Gu ◽  
Na Li ◽  
Junru Wang
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Apoptosis Induction ◽  
Synthesis And Biological Evaluation

A series of novel bivalent β-carbolines were synthesized and evaluated for their anti-proliferative activities on a panel of cancer cell lines, apoptosis induction and cell cycle effects.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

scholarly journals Click Synthesis, Anticancer Activity, and Molecular Docking Investigation of some Functional 1,2,3-triazole Derivatives

2021 ◽  
Vol 12 (6) ◽  
pp. 7633-7667
Keyword(s):  
Cell Cycle ◽  
Molecular Docking ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Cancer Cell Lines ◽  
Reference Drug ◽  
Active Inhibitor ◽  
Triazole Derivatives

1,2,3-triazole skeleton is a privileged building block for the discovery of new promising anticancer agents. In this report, new 1,4-disubstituted 1,2,3-triazoles with the bioisoster triazole moiety were straightforwardly prepared under copper-catalyzed azide-alkyne [3+2] cycloaddition reactions (CuAAC) regime using a variety of both functional organic azides and terminal alkynes. The resulting functional 1,4-disubstituted 1,2,3-triazole compounds were fully characterized and subsequently tested for their antiproliferative activity against four different cancer cell lines. The cytotoxicity tests carried out with these 1,2,3-triazole derivatives show average IC50 values ranging from 15 to 50 µM by comparison with the standard reference drug, namely doxorubicin. The phosphonate 1,2,3-triazole derivative was found to exhibit the best antiproliferative activity among the studied compounds against the HT-1080 cell lines. It was chosen to evaluate its mode of action in these cancer cell lines. The cell cycle study showed that the phosphonate derivative, compound 8, is the most active inhibitor of the cell cycle at the G0/G1 phase, inducing apoptosis independently of Caspase-3 and causing an increase in the mitochondrial membrane potential (ΔΨm) in the HT-1080 cell lines. Molecular docking studies of this phosphonate derivative into the MMP-2 and MMP-9 metalloproteinases receptors demonstrated the relevance of triazole scaffolds and the pendant phosphonate group in establishing -anion, -alkyl and hydrogen bonding type interactions with residual components in the active MMP pocket.

scholarly journals Apoptosis Induction, Cell Cycle Arrest and in Vitro Anticancer Activity of Gonothalamin in a Cancer Cell Lines

2012 ◽  
Vol 13 (10) ◽  
pp. 5131-5136 ◽  
Author(s):  
Aied M. Alabsi ◽  
Rola Ali ◽  
Abdul Manaf Ali ◽  
Sami Abdo Radman Al-Dubai ◽  
Hazlan Harun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Apoptosis Induction ◽  
Cycle Arrest

Terpyridine Copper(II) Complexes as Potential Anticancer Agents by Inhibiting Cell Proliferation, Blocking Cell Cycle and Inducing Apoptosis in BEL-7402 Cells

2022 ◽  
Author(s):  
Yunqiong Gu ◽  
Yu-Jun Zhong ◽  
Mei-Qi Hu ◽  
Huan-Qing Li ◽  
Kun Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines

Four mononuclear terpyridine complexes [Cu(H-La)Cl2]·CH3OH (1), [Cu(H-La)Cl]ClO4 (2), [Cu(H-Lb)Cl2]·CH3OH (3), and [Cu(H-Lb)(CH3OH)(DMSO)](ClO4)2 (4) were prepared and fully characterized. Complexes 14 exhibited higher cytotoxic activity against several tested cancer cell lines...

Synthesis, Antiproliferative activity, and apoptotic profile of New Derivatives from the Meta Stable Benzoxazinone Scaffold

2021 ◽  
Vol 21 ◽  
Author(s):  
Amira El-Sayed ◽  
Maher El-Hashash ◽  
Wael El-Sayed
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Human Fibroblasts ◽  
Cancer Cell Lines ◽  
Selectivity Index ◽  
Human Cancer Cell Lines

Background: Cancer exerts a huge strain on the health system. The emerging resistance to the current chemotherapies demands the continuous development of new anticancer agents with lower cost, higher efficacy, and greater specificity. Objective: Development of selective small molecules targeted anticancer agents Methods: The behavior of benzoxazinone 2 towards nitrogen nucleophiles such as hydrazine hydrate, formamide, ethanolamine, aromatic amines, and thiosemcarbazide was described. The behavior of the amino quinazolinone 3 towards carbon electrophiles and P2S5 was also investigated. The antiproliferative activity of 17 new benzoxazinone derivatives was examined against the growth of three human cancer cell lines; liver HepG2, breast MCF-7, and colon HCT-29, in addition to the normal human fibroblasts WI-38 and the selectivity index was calculated. The possible molecular pathways such as the cell cycle and apoptosis were investigated. Results: Derivatives 3, 7, 8, 10, 13, and 15 had a significant (less than 10 µM) antiproliferative activity against the three cancer cell lines investigated. Derivative 7 showed the best antiproliferative profile comparable to that of doxorubicin. The selectivity index for all the effective derivatives ranged from ~5-12 folds indicating high selectivity against the cancer cells. Derivative 15 caused ~ 7-fold and 8-fold inductions in the expression of p53 and caspase3, respectively. It also caused a ~ 60% reduction in the expression of both topoisomerase II (topoII) and cyclin-dependent kinase 1 (cdk1). Derivatives 3, 7, and 8 had a similar profile; ~ 6-8-fold increases in the expression of p53 and caspase3 but these compounds were devoid of any significant effect on the expression of topoII and cdk1. Derivatives 10 and 13 were also similar and resulted in a ~6-fold elevation in the expression of caspase3, and more than 60% downregulation in the expression of topoII. The results of the gene expression of topoII and caspase 3 were confirmed by the measurement of the topoII concentration and caspase3 activity in the HepG2 cells. Conclusion: Six derivatives exerted their antiproliferative activity by arresting the cell cycle (decreasing cdk1), preventing the DNA duplication (downregulating topo II), and by inducing apoptosis (inducing p53 and caspase3). One common feature in all the six active derivatives is the presence of free amino group. These compounds have merit for further investigations.

scholarly journals Synthesis and biological evaluation of phosphatidylcholines with cinnamic and 3-methoxycinnamic acids with potent antiproliferative activity

RSC Advances ◽  
2018 ◽  
Vol 8 (62) ◽  
pp. 35744-35752 ◽  
Author(s):  
Marta Czarnecka ◽  
Marta Świtalska ◽  
Joanna Wietrzyk ◽  
Gabriela Maciejewska ◽  
Anna Gliszczyńska
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Synthesis And Biological Evaluation

A series of eight novel phosphatidylcholines containing CA or 3-OMe-CA acids (3a-b, 5a-b, 9a-b, 10a-b) at sn-1 and/or sn-2 positions were synthesized and tested for their antiproliferative activity against selected cancer cell lines.

scholarly journals Synthesis and Biological Evaluation of New Antitubulin Agents Containing 2-(3′,4′,5′-trimethoxyanilino)-3,6-disubstituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine Scaffold

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1690
Author(s):  
Romeo Romagnoli ◽  
Filippo Prencipe ◽  
Paola Oliva ◽  
Barbara Cacciari ◽  
Jan Balzarini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mononuclear Cells ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Pyridine Derivative ◽  
Tubulin Polymerization ◽  
Dependent Manner

Two novel series of compounds based on the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine and 4,5,6,7-tetrahydrobenzo[b]thiophene molecular skeleton, characterized by the presence of a 3′,4′,5′-trimethoxyanilino moiety and a cyano or an alkoxycarbonyl group at its 2- or 3-position, respectively, were designed, synthesized, and evaluated for antiproliferative activity on a panel of cancer cell lines and for selected highly active compounds, inhibition of tubulin polymerization, and cell cycle effects. We have identified the 2-(3′,4′,5′-trimethoxyanilino)-3-cyano-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivative 3a and its 6-ethoxycarbonyl homologue 3b as new antiproliferative agents that inhibit cancer cell growth with IC50 values ranging from 1.1 to 4.7 μM against a panel of three cancer cell lines. Their interaction with tubulin at micromolar levels leads to the accumulation of cells in the G2/M phase of the cell cycle and to an apoptotic cell death. The cell apoptosis study found that compounds 3a and 3b were very effective in the induction of apoptosis in a dose-dependent manner. These two derivatives did not induce cell death in normal human peripheral blood mononuclear cells, suggesting that they may be selective against cancer cells. Molecular docking studies confirmed that the inhibitory activity of these molecules on tubulin polymerization derived from binding to the colchicine site.

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