Half-Lantern Cyclometalated Platinum(II) Complexes as Potent Anticancer Agents: Molecular Docking, Apoptosis, Cell Cycle Analysis and Cytotoxic Activity Evaluations

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.

Download Full-text

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

Dalton Transactions ◽

10.1039/d1dt02988f ◽

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...

Download Full-text

2-Anilinopyrimidine derivatives: Design, synthesis, in vitro anti-proliferative activity, EGFR and ARO inhibitory activity, cell cycle analysis and molecular docking study

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.103798 ◽

2020 ◽

Vol 99 ◽

pp. 103798 ◽

Cited By ~ 1

Author(s):

Omaima M. AboulWafa ◽

Hoda M.G. Daabees ◽

Waleed A. Badawi

Keyword(s):

Cell Cycle ◽

Molecular Docking ◽

Inhibitory Activity ◽

Proliferative Activity ◽

Docking Study ◽

Cell Cycle Analysis ◽

Molecular Docking Study ◽

Design Synthesis

Download Full-text

Synthesis, Anticancer Evaluation, and Molecular Docking of Hexahydroquinoline Derivatives as Mcl-1 Inhibitors and Apoptosis Inducers

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666211021133558 ◽

2021 ◽

Vol 21 ◽

Author(s):

Nishith Teraiya ◽

Subhas S Karki ◽

Ashlesha Chauhan

Keyword(s):

Cell Cycle ◽

Anticancer Agents ◽

Caspase 3 ◽

Cell Cycle Analysis ◽

Caspase 9 ◽

Spectral Techniques ◽

Apoptotic Protein ◽

Potent Inhibition ◽

Activation Assay ◽

New Compounds

Background: Hexahydroquinoline as a small molecule was reported for good cytotoxicity and affinity towards Mcl-1. Hence, new compounds were explored as Mcl-1 inhibitors to be potent anticancer agents. Objective: Compounds were synthesized and screened for cytotoxicity. The active compound was evaluated for cell cycle analysis, Mcl-1 inhibition, caspase-3, and caspase-9 activation. Further compounds were docked with Mcl-1 to confirm the mechanism of cytotoxicity. Methods: Compounds were confirmed by spectral techniques and screened for cytotoxicity at National Cancer Institute (USA). The active derivatives were screened by SRB and MTT. In addition, the potent compound was studied for apoptosis and cell cycle analysis by PI staining, Mcl-1 inhibition by TR-FRET assay, and activation assay of caspase-3 and caspase-9 with the Elisa technique. Results: Compounds 6a and 6b exhibited the highest growth inhibition of 86.28% and 93.20% against SR and HOP-62, respectively. Compound 6a showed higher cytotoxicity (IC50 = 0.4 µM) against THP-1 and HL-60. It showed 15-fold higher apoptosis compared to control by arresting cells at the Sub-G1 in the cell cycle. It also showed a potent inhibition with IC50 of 1.5 µM against the anti-apoptotic protein Mcl-1, which may induce apoptosis. Furthermore, apoptosis was evidenced by an increase in cleaved caspase-3 and caspase-9 to 4.20 and 3 folds, respectively higher than control. The docking score of compound 6a was in good agreement with the Mcl-1 inhibition assay. Conclusion: Compound 6a inhibited anti-apoptotic protein Mcl-1 and induced activation of pro-apoptotic proteins caspase-3 and caspase-9. These dual results suggested the mechanism of apoptosis and cytotoxicity.

Download Full-text

Isolation and Cytotoxic Activity of Phyllocladanes from the Roots of Acacia schaffneri (Leguminosae)

Molecules ◽

10.3390/molecules25173944 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3944

Author(s):

José de Jesús Manríquez-Torres ◽

Marco Antonio Hernández-Lepe ◽

José Román Chávez-Méndez ◽

Susana González-Reyes ◽

Idanya Rubí Serafín-Higuera ◽

...

Keyword(s):

Cell Cycle ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Spectroscopic Properties ◽

Cancer Cell Lines ◽

Moderate Activity ◽

Cycle Arrest ◽

Ic50 Values

In research on natural molecules with cytotoxic activity that can be used for the development of new anticancer agents, the cytotoxic activity of hexane, chloroform, and methanol extracts from the roots of Acacia schaffneri against colon, lung, and skin cancer cell lines was explored. The hexane extract showed the best activity with an average IC50 of 10.6 µg mL−1. From this extract, three diterpenoids, phyllocladan-16α,19-diol (1), phyllocladan-16α-ol (2), and phylloclad-16-en-3-ol (3), were isolated and characterized by their physical and spectroscopic properties. Diterpenoids 1 and 2 were tested against the same cancer cell lines, as well as their healthy counterparts, CCD841 CoN, MRC5, and VH10, respectively. Compound 1 showed moderate activity (IC50 values between 24 and 70 μg mL−1), although it showed a selective effect against cancer cell lines. Compound 2 was practically inactive. The cytotoxicity mechanism of 1 was analyzed by cell cycle, indicating that the compound induces G0/G1 cell cycle arrest. This effect might be generated by DNA alkylation damage. In addition, compound 1 decreased migration of HT29 cells.

Download Full-text

Cytotoxic Activity of Cycloartane Triterpenoids from Sphaerophysa Salsula

Natural Product Communications ◽

10.1177/1934578x0900400107 ◽

2009 ◽

Vol 4 (1) ◽

pp. 1934578X0900400

Author(s):

Dan Wang ◽

Zhongjun Ma

Keyword(s):

Cell Cycle ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Western Blotting ◽

Cancer Cell Lines ◽

Cell Cycle Analysis ◽

Cycloartane Triterpenoids ◽

Sphaerophysa Salsula ◽

Mcf 7

The cytotoxicity of three cycloartane triterpenoids, 9, 19-cycloart-7β, 24R, 25- triol-1-en-3-one (1), 9, 19-cycloart-7β, 24R, 25-triol-1-en-3-one 25-O-β-D-glucopynanoside (2), and 25-O-β-D-arabinopyranosyl-(1→4)- β-D-glucopyranosyl-9, 19-cycloart-7β, 24R, 25-triol-1-en-3-one (3), isolated from Sphaerophysa salsula was investigated on SF188, U87wt, MCF-7, and H460 cancer cell lines. Compound 1 showed the strongest activity. Cell cycle analysis was employed to elucidate the cytotoxicity on the tested U87wt cells, which led to G2/M arrest. In addition, from the Western blotting experiments, the expression of P21 is increased.

Download Full-text

Cytotoxic Activity and Cell Cycle Analysis of Quinoline Alkaloids Isolated fromHaplophyllum canaliculatumBoiss.

Planta Medica ◽

10.1055/s-0029-1185807 ◽

2009 ◽

Vol 75 (14) ◽

pp. 1509-1516 ◽

Cited By ~ 9

Author(s):

Pegah Varamini ◽

Katayoun Javidnia ◽

Mohammad Soltani ◽

Ahmad Mehdipour ◽

Abbas Ghaderi

Keyword(s):

Cell Cycle ◽

Cytotoxic Activity ◽

Cell Cycle Analysis ◽

Quinoline Alkaloids

Download Full-text

Half-lantern Cyclometalated Platinum(II) Complexes as Anticancer Agents: Molecular docking, Apoptosis, Cell Cycle Analysis and Cytotoxic Activity Evaluations

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210713112105 ◽

2021 ◽

Vol 21 ◽

Author(s):

Fatemeh Hajipour ◽

Masoud Mahdavinia ◽

Masood Fereidoonnezhad

Keyword(s):

Cell Cycle ◽

Molecular Docking ◽

Comet Assay ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Human Lung ◽

Cancer Cell Line ◽

Cell Cycle Analysis ◽

Mcf 7

Background and Objective: In the design of modern metal-based anticancer drugs, platinum-based complexes have gained growing interest. In this study, the anticancer activity of half-lantern cyclometalated Pt(II)‒Pt(II) complexes were was evaluated using MTT, apoptosis, cell cycle analysis, and DNA binding studies. Materials and Methods: The cytotoxicity of Pt(II)‒Pt(II) complexes were evaluated against different cancer cell lines such as human lung (A549), breast (MCF-7, and MDA-MB-231), ovarian (SKOV-3), and colon (HT-29) as well as normal breast (MCF-10A), and human lung fibroblast MRC-5 cells using MTT assay. BioLegend's PE Annexin V Apoptosis Detection Kit with 7AAD was applied to assess the apoptotic effects of 1A, and 1B compound against MCF-7, and A549 cell lines. Cell cycle analysis was determined using the flowcytometry method. The interaction of compounds with four different DNA structures with PDB codes (1BNA, 1LU5, 3CO3, and 198D) has been investigated by molecular docking. To achieve binding to DNA experimentally, the electrophoresis mobility shift assay and comet assay was applied. Results: In the evaluation of cytotoxic effects, 1A showed the highest cytotoxicity among the studied compounds, and it showed higher potency with more selectivity against normal cell lines than cisplatin. This compound had IC50 of 7.24, 2.21, 1.18, 2.71, 10.65, 18.32 and 49.21 μM against A549, SKOV3, HT29, MCF-7, MDA-MB-231, MRC-5, and MCF-10A, respectively, whereas cisplatin had IC50 of 9.75, 19.02, 107.23, 15.20, 18.09, 14.36, and 24.21 μm, respectively, on the same cell lines. In order to check the DNA binding activity of 1A, and 1B, electrophoretic mobility was also conducted, which indicated that the binding of these compounds led to a slight change in electrophoretic mobility to DNA. The migration of chromosomal DNA from the nucleus in the form of a tail or comet was executed in the comet assay of 1A on MCF-7. Examination of apoptosis of 1A, and 1B on the MCF-7 cancer cell line, showed that it could increase induction of apoptosis in this cancerous cell in a concentration-dependent manner. Investigating the effect of 1A using cell cycle analysis on MCF-7 cancer cell line showed that this complex affects the stage G1 and S of the cell cycle. Conclusion: 1A has the potential to play a significant role in future biopharmaceutical studies.

Download Full-text