Synthesis and evaluation of bis(imino)anthracene derivatives as G-quadruplex ligands

Coban, Tomris; Robertson, Cameron; Schwikkard, Sianne; Singer, Richard J.; LeGresley, Adam

doi:10.1039/d0md00428f

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…In addition to the experimental assays, computational studies were used to examine the insulin residues that might be able to interact with the synthesized compounds. To investigate this issue more closely, use was made of two tools, namely, CB-Dock and Molegro Virtual Docker (MVD), which have been considered more in the literature. − While using both tools, the number of insulin binding pores was considered to be 5.0.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms behind the Fibrillation and Toxicity of Insulin Fibrils on Neuron Cells by Engineered Curcumin Analogs

Akbarian

Bahmani

Chen

et al. 2022

ACS Chem. Neurosci.

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Among foods, the use of plant derivatives as promising drugs and/or excipients has been considered from various perspectives. In the present study, curcumin, which is one of the most important plant derivatives for biological uses, and four curcumin-based pyrido[2,3-d]pyrimidine analogs (C2-C5) were used for investigating the mechanism of insulin fibrillation and evaluating the cytotoxicity of insulin fibrils. The synthesized analogs differed in terms of hydrophobicity and electrostatic charge. The analogs with more hydrophobicity (C1 and C4) in both acidic and neutral environments were able to reduce the rate of insulin fibrillation and the degree of cross-linking in the produced fibrils. Additionally, the toxicity of these fibrils for neural cells (N2a cell line) was very low. However, they did not show any significant effects on the toxicity of non-neural cells (HEK293 cell line), indicating the effect of the biochemical surface diversity on determining the vulnerability to fibrils and even the mechanism of action of additives on cell line survival. Although negatively charged analogs were able to reduce insulin fibrillation in the acidic environment, they indicated an opposite effect in the neutral environment. The resultant fibrils in the acidic medium appeared with a well-distinguished filament, but they were very close at neutral pH levels. Moreover, such fibrils indicated very poor toxicity against the N2a cell line and had no significant effects on HEK293 cells. Considering the docking studies, by creatively using the size exclusion chromatography, it was suggested that analogs C2 and C3 were capable of binding to the C-terminal end of the insulin B chain (low affinity) and HisB10 (high affinity). Hence, it was suggested that different compounds could play different protecting and/or destroying roles in cell toxicity by blocking some ligands at the surface of neuron cells.

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Section: Methodsmentioning

confidence: 99%

Mechanisms behind the Fibrillation and Toxicity of Insulin Fibrils on Neuron Cells by Engineered Curcumin Analogs

Akbarian

Bahmani

Chen

et al. 2022

ACS Chem. Neurosci.

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“…Choosing the right size means that the docking method has ample room to investigate various ligand conformations and orientations within the binding site. The server is designed to interact with AutoDock Vina and has been meticulously tuned to produce models with a success rate of more than 70 % [ [ 62 , 63 ]. The ligand is taken in pdb format and the selected proteins is obtained in pdb format from RCSB protein data bank.…”

Section: Molecular Dockingmentioning

confidence: 99%

Synthesis, characterization, DFT studies and evaluation of the potential anti-tumour activity of nicotinic hydrazide based Schiff base using in vitro and molecular docking techniques

Preethi,

Vijukumar,

AnilaRaj

et al. 2024

Heliyon

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“…We wished to investigate the preclinical potential of a panel of related (E)-9-(2-nitrovinyl)anthracenes as antiproliferative compounds in CLL, which is a more common but related B-cell malignancy. Nitro-group-containing compounds may induce selective cancer cell toxicity by diverse mechanisms [46] such as topoisomerase inhibition [47], histone deacetylase inhibition [48], DNA alkylation [49] or tubulin polymerisation inhibition [50][51][52], while anthracene-containing compounds are reported to interact selectively with G-quadruplex structures and inhibit telomerase [53]. The objective of this research was the investigation of a series of (E)-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds for antiprolifertive evaluation in BL and CLL cell lines and is arranged as follows:…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Pro-Apoptotic Effects of Nitrovinylanthracenes and Related Compounds in Chronic Lymphocytic Leukaemia (CLL) and Burkitt’s Lymphoma (BL)

Byrne,

Bright,

McKeown

et al. 2023

Molecules

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Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of (E)-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt’s lymphoma (BL) cell lines, a rare form of non-Hodgkin’s immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL. The series of structurally diverse nitrostyrenes was synthesised via Henry–Knoevenagel condensation reactions. Single-crystal X-ray analysis confirmed the structure of (E)-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene (19f) and the related 4-(anthracen-9-yl)-1H-1,2,3-triazole (30a). The (E)-9-(2-nitrovinyl)anthracenes 19a, 19g and 19i–19m were found to elicit potent antiproliferative effects in both BL cell lines EBV−MUTU-1 (chemosensitive) and EBV+ DG-75 (chemoresistant) with >90% inhibition at 10 μM. Selected (E)-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC50 values of 0.17 μM (HG-3) and 1.3 μM (PGA-1) for compound 19g. The pro-apoptotic effects of the most potent compounds 19a, 19g, 19i, 19l and 19m were demonstrated in both CLL cell lines HG-3 and PGA-1. The (E)-nitrostyrene and (E)-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL.

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Synthesis and evaluation of bis(imino)anthracene derivatives as G-quadruplex ligands

Abstract: The synthesis of a small number of bis(imino)anthracene derivatives is reported. They were evaluated via NMR for binding efficacy to the G-quadruplex-forming oligonucleotide sequence (TTGGGTT) and show activity against the HeLa cancer cell line.

Cited by 3 publications

References 37 publications

Mechanisms behind the Fibrillation and Toxicity of Insulin Fibrils on Neuron Cells by Engineered Curcumin Analogs

Mechanisms behind the Fibrillation and Toxicity of Insulin Fibrils on Neuron Cells by Engineered Curcumin Analogs

Synthesis, characterization, DFT studies and evaluation of the potential anti-tumour activity of nicotinic hydrazide based Schiff base using in vitro and molecular docking techniques

Synthesis and Pro-Apoptotic Effects of Nitrovinylanthracenes and Related Compounds in Chronic Lymphocytic Leukaemia (CLL) and Burkitt’s Lymphoma (BL)

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