Amides of pyrrole- and thiophene-fused anthraquinone derivatives: A role of the heterocyclic core in antitumor properties

Тихомиров, А. С.; Litvinova, Valeriya А.; Andreeva, Daria V.; Цветков, В. Б.; Dezhenkova, Lyubov G.; Volodina, Yulia L.; Kaluzhny, Dmitry N.; Treshalin, Ivan D.; Schols, Dominique; Ramonova, Alla A.; Moisenovich, Mikhail M.; Shtil, Alexander А.; Shchekotikhin, Andrey E.

doi:10.1016/j.ejmech.2020.112294

Cited by 22 publications

(8 citation statements)

References 59 publications

(81 reference statements)

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“…The pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(O-Me) fluoromethyl ketone (z-VAD-FMK) was from Selleckchem, Houston, TX, USA. The cytotoxicity of metal NPs and Cu–organic complexes alone or in combinations with NAC, ascorbate, or α-tocopherol was determined in MTT assays [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Tsymbal

Moiseeva

Agadzhanian

et al. 2021

IJMS

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Copper-containing agents are promising antitumor pharmaceuticals due to the ability of the metal ion to react with biomolecules. In the current study, we demonstrate that inorganic Cu2+ in the form of oxide nanoparticles (NPs) or salts, as well as Cu ions in the context of organic complexes (oxidation states +1, +1.5 and +2), acquire significant cytotoxic potency (2–3 orders of magnitude determined by IC50 values) in combinations with N-acetylcysteine (NAC), cysteine, or ascorbate. In contrast, other divalent cations (Zn, Fe, Mo, and Co) evoked no cytotoxicity with these combinations. CuO NPs (0.1–1 µg/mL) together with 1 mM NAC triggered the formation of reactive oxygen species (ROS) within 2–6 h concomitantly with perturbation of the plasma membrane and caspase-independent cell death. Furthermore, NAC potently sensitized HCT116 colon carcinoma cells to Cu–organic complexes in which the metal ion coordinated with 5-(2-pyridylmethylene)-2-methylthio-imidazol-4-one or was present in the coordination sphere of the porphyrin macrocycle. The sensitization effect was detectable in a panel of mammalian tumor cell lines including the sublines with the determinants of chemotherapeutic drug resistance. The components of the combination were non-toxic if added separately. Electrochemical studies revealed that Cu cations underwent a stepwise reduction in the presence of NAC or ascorbate. This mechanism explains differential efficacy of individual Cu–organic compounds in cell sensitization depending on the availability of Cu ions for reduction. In the presence of oxygen, Cu+1 complexes can generate a superoxide anion in a Fenton-like reaction Cu+1L + O2 → O2−.+ Cu+2L, where L is the organic ligand. Studies on artificial lipid membranes showed that NAC interacted with negatively charged phospholipids, an effect that can facilitate the penetration of CuO NPs across the membranes. Thus, electrochemical modification of Cu ions and subsequent ROS generation, as well as direct interaction with membranes, represent the mechanisms of irreversible membrane damage and cell death in response to metal reduction in inorganic and organic Cu-containing compounds.

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Section: Methodsmentioning

confidence: 99%

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Tsymbal

Moiseeva

Agadzhanian

et al. 2021

IJMS

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“…117 Perry et al synthesized a series of 1,4-and 2,6-di functionalized amido anthracene-9,10-diones and examined their cytotoxicity along with telomerase inhibitory activity. Among the synthesized, piperidine 2, 6-anthraquinone derivative (88) and N,N 0 -dimethiodide derivative (89) elicited good enzymatic inhibition of telomerase with IC 50 values of 4.5 and 9.4 mM, respectively. 118 Huang et al reported the synthesis of 1,5-bisthioanthraquinones and 1,5-bisacyloxyanthraquinones and examined their telomerase activity along with the expression of telomerase.…”

Section: Telomerase Inhibitorsmentioning

confidence: 99%

“…From in vivo studies, it was concluded that the compound enhanced the lifespan of mice carrying P388 lymphoma transplants hinting at tumour inhibition. 89 Selaginella tamariscina is a traditional Chinese herb used to treat diseases like cancer, diabetes, and hepatitis. Rui Liu et al isolated four new anthraquinone compounds selaginones A, selaginones B, triarylbenzophenone analogue, selagibenzophenone B from S. tamariscina herb.…”

Section: Development Of Non-specific Cytotoxic Anthraquinone Derivativesmentioning

confidence: 99%

Journey of anthraquinones as anticancer agents – a systematic review of recent literature

et al. 2021

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“…Nonetheless, the foremost synthetic challenge in this field is to design and synthesize new polytopic ligands with appropriate donor groupings placed strategically in place for metal coordination. In general, pyrrole, thiophene, and their organic and metal cluster derivatives are recognized to present a wide range of biological activities [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Therefore, the design and synthesis of novel ligands containing the thiophene and pyrrole rings have attracted great interest.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Tritopic Hydrazone Ligands: Spectroscopy, Biological Activity, DFT, and Molecular Docking Studies

et al. 2022

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Polytopic organic ligands with hydrazone moiety are at the forefront of new drug research among many others due to their unique and versatile functionality and ease of strategic ligand design. Quantum chemical calculations of these polyfunctional ligands can be carried out in silico to determine the thermodynamic parameters. In this study two new tritopic dihydrazide ligands, N’2, N’6-bis[(1E)-1-(thiophen-2-yl) ethylidene] pyridine-2, 6-dicarbohydrazide (L1) and N’2, N’6-bis[(1E)-1-(1H-pyrrol-2-yl) ethylidene] pyridine-2, 6-dicarbohydrazide (L2) were successfully prepared by the condensation reaction of pyridine-2, 6-dicarboxylic hydrazide with 2-acetylthiophene and 2-acetylpyrrole. The FT-IR, 1H, and 13C NMR, as well as mass spectra of both L1 and L2, were recorded and analyzed. Quantum chemical calculations were performed at the DFT/B3LYP/cc-pvdz/6-311+ G (d, p) level of theory to study the molecular geometry, vibrational frequencies, and thermodynamic properties including changes of ∆H, ∆S, and ∆G for both the ligands. The optimized vibrational frequency and (1H and 13C) NMR obtained by B3LYP/cc-pvdz/6-311 + G (d, p) showed good agreement with experimental FT-IR and NMR data. Frontier molecular orbital (FMO) calculations were also conducted to find the HOMO, LUMO, and HOMO–LUMO gaps of the two synthesized compounds. To investigate the biological activities of the ligands, L1 and L2 were tested using in vitro bioassays against some Gram-negative and Gram-positive bacteria and fungus strains. In addition, molecular docking was used to study the molecular behavior of L1 and L2 against tyrosinase from Bacillus megaterium. The outcomes revealed that both L1 and L2 can suppress microbial growth of bacteria and fungi with variable potency. The antibacterial activity results demonstrated the compound L2 to be potentially effective against Bacillus megaterium with inhibition zones of 12 mm while the molecular docking study showed the binding energies for L1 and L2 to be −7.7 and −8.8 kcal mol−1, respectively, with tyrosinase from Bacillus megaterium.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬

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Amides of pyrrole- and thiophene-fused anthraquinone derivatives: A role of the heterocyclic core in antitumor properties

Cited by 22 publications

References 59 publications

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Journey of anthraquinones as anticancer agents – a systematic review of recent literature

Synthesis of Novel Tritopic Hydrazone Ligands: Spectroscopy, Biological Activity, DFT, and Molecular Docking Studies

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