Oxamusplatin: a cytotoxic Pt(<scp>ii</scp>) complex of a nitrogen mustard with resistance to thiol based sequestration displays enhanced selectivity towards cancer

Maji, Moumita; Karmakar, Subhendu; Ruturaj,; Gupta, Arnab; Mukherjee, Arindam

doi:10.1039/c9dt04269e

Cited by 14 publications

(24 citation statements)

References 51 publications

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“…As a result, the cytotoxicity of the complex is more effective than free BBHMP and NA. In comparison with previously reported literature IC 50 data [63,[71][72][73], the synthesized complex was evaluated to be less effective toward the DU145 and MCF7.…”

Section: Cytotoxicity Resultsmentioning

confidence: 94%

Synthesis and Biological Activity of a New Pt(II) Complex Involving 4-bromo-2,6-bis-hydroxymethyl-phenol and Nicotinamide

Altun

Yoruç

Boz

2021

Preprint

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In the presented study, Pt(II) complex including 4-Bromo-2,6-bis-hydroxymethyl-phenol (BBHMP) and nicotinamide (NA) was synthesized and structurally analyzed by using spectral and thermal analysis methods. The BBHMP and its Pt(II) complex involving BBHMP and NA were investigated for their antimicrobial, cytotoxicity, gen expression and antioxidant properties. The antimicrobial activity results showed that the platinum complex displayed moderate antibacterial and antifungal activities. The cytotoxicity of the BBHMP and platinum complex were determined against human prostate (DU145) and breast (MCF7) cancer cell lines by applying MTT assay. Cytotoxicity results suggest that the Pt(II) complex exhibited moderate cytotoxicity against growth of used cancer cell lines when compared with the reference drug cisplatin. Gen expression results proved that Pt(II) complex is a special bioactive chemical constituent and potential anticancer agent. In addition, the complex demonstrated important antioxidant activity.

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Section: Cytotoxicity Resultsmentioning

confidence: 94%

Synthesis and Biological Activity of a New Pt(II) Complex Involving 4-bromo-2,6-bis-hydroxymethyl-phenol and Nicotinamide

Altun

Yoruç

Boz

2021

Preprint

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“…The Fourier transform infrared (FT-IR) spectra were recorded using a PerkinElmer SPECTRUM RX I spectrometer in KBr pellets. 1 H NMR, 13 C NMR, and HMQC spectra were recorded using either a 400 MHz JEOL ECS or 500 MHz Bruker Avance III spectrometer at room temperature (24−27 °C). All of the 13 C NMR spectra reported are proton-decoupled.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Platinum drugs have displayed high cure rates for testicular cancer and are used to treat various other tumors, viz., prostate, colon, ovarian, esophageal, bladder, head and neck, and nonsmall cell lung cancer. − Platinum drugs are also known for their poor tumor selectivity, serious side effects, and intrinsic and/or acquired resistance, making them ineffective for treatment against several tissue types. ,, Thus, in spite of its clinical success, the deleterious side effects of cisplatin have led to the search for new anticancer agents with improved therapeutics. The goal of the modern design by changing the metal and tuning ligand properties encompasses the reduction of adverse side effects, activation by external stimuli, and a focus on targets other than the nucleus to avoid mutagenic character and improve delivery. − Metal complexes with potential apart from platinum(II/IV) include gallium(II) and ruthenium(II/III). − Gallium(III) nitrate has been effective against lymphoma and bladder cancer . Gallium(III) maltolate and tris(8-quinolinolato)gallium(III) have shown efficiency against hepatocellular carcinoma and renal carcinoma, respectively. ,, …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Cytotoxicity of Morpholine-Containing Ruthenium(II) p-Cymene Complexes

et al. 2021

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Morpholine motif is an important pharmacophore and, depending on the molecular design, may localize in cellular acidic vesicles. To understand the importance of the presence of pendant morpholine in a metal complex, six bidentate N,O-donor ligands with or without a pendant morpholine unit and their corresponding ruthenium(II) p-cymene complexes (1–6) are synthesized, purified, and structurally characterized by various analytical methods including X-ray diffraction. Complexes 2–4 crystallized in the P21/c space group, whereas 5 and 6 crystallized in the P1̅ space group. The solution stability studies using 1H NMR support instantaneous hydrolysis of the native complexes to form monoaquated species in a solution of 3:7 (v/v) dimethyl sulfoxide-d 6 and 20 mM phosphate buffer (pH* 7.4, containing 4 mM NaCl). The monoaquated complexes are stable for at least up to 24 h. The complexes display excellent in vitro antiproliferative activity (IC50 ca. 1–14 μM) in various cancer cell lines, viz., MDA-MB-231, MiaPaCa2, and Hep-G2. The presence of the pendant morpholine does not improve the dose efficacy, but rather, with 2-[[(2,6-dimethylphenyl)imino]methyl]phenol (HL1) and its pendant morpholine analogue (HL3) giving complexes 1 and 3, respectively, the antiproliferative activity was poorer with 3. MDA-MB-231 cells treated with the complexes show that the acidic vesicles remain acidic, but the population of acidic vesicles increases or decreases with time of exposure, as observed from the dispersed red puncta, depending on the complex used. The presence of the 2,6-disubstituted aniline and the naphthyl group seems to improve the antiproliferative dose. The complex treated MDA-MB-231 cells show that cathepsin D, which is otherwise present in the cytosolic lysosomes, translocates to the nucleus as a result of exposure to the complexes. Irrespective of the presence of a morpholine motif, the complexes do not activate caspase-3 to induce apoptosis and seem to favor the necrotic pathway of cell killing.

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“…Platinum compounds play a prevalent role in metal-based anticancer therapies, with cisplatin, carboplatin, and oxaliplatin used all over the world in clinics despite general low selectivity and drug resistance often limiting their efficacy [4,5]. To date, the efforts of the scientific community have multiplied to prepare increasingly effective agents, aimed at reducing the numerous and unpleasant side effects of cisplatin and its close derivatives [6][7][8][9][10][11][12][13][14][15][16]. One of the most successful strategies is the introduction of bio-active molecules in the coordination environment of the metal, capable of increasing its versatility and selectivity [17,18].…”

Section: Introductionmentioning

confidence: 99%

Square-Planar vs. Trigonal Bipyramidal Geometry in Pt(II) Complexes Containing Triazole-Based Glucose Ligands as Potential Anticancer Agents

Annunziata

Liberti

Bedini

et al. 2021

IJMS

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This article describes the synthesis, characterization, and biological activity of novel square-planar cationic platinum(II) complexes containing glucoconjugated triazole ligands and a comparison with the results obtained from the corresponding five-coordinate complexes bearing the same triazole ligands. Stability in solution, reactivity with DNA and small molecules of the new compounds were evaluated by NMR, fluorescence, and UV–vis absorption spectroscopy, together with their cytotoxic action against pairs of immortalized and tumorigenic cell lines. The results show that the square-planar species exhibit greater stability than the corresponding five-coordinate ones. Furthermore, although the square-planar complexes are less cytotoxic than the latter ones, they exhibit a certain selectivity. These results simultaneously demonstrate that overall stability is a fundamental prerequisite for preserving the performance of the agents and that coordinative saturation constitutes a point in favor of their biological action.

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Oxamusplatin: a cytotoxic Pt(ii) complex of a nitrogen mustard with resistance to thiol based sequestration displays enhanced selectivity towards cancer

Abstract: Oxamusplatin shows enhanced selectivity towards cancer, targets cellular DNA, disrupts the microtubule network and strongly resists sequestration by deactivating agents, glutathione, ATP7B or phosphoglycoproteins.

Cited by 14 publications

References 51 publications

Synthesis and Biological Activity of a New Pt(II) Complex Involving 4-bromo-2,6-bis-hydroxymethyl-phenol and Nicotinamide

Synthesis and Biological Activity of a New Pt(II) Complex Involving 4-bromo-2,6-bis-hydroxymethyl-phenol and Nicotinamide

Synthesis, Characterization, and Cytotoxicity of Morpholine-Containing Ruthenium(II) p-Cymene Complexes

Square-Planar vs. Trigonal Bipyramidal Geometry in Pt(II) Complexes Containing Triazole-Based Glucose Ligands as Potential Anticancer Agents

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