DNA binding and antitumor activities of platinum(IV) and zinc(II) complexes with some S-alkyl derivatives of thiosalicylic acid

Silconi, Žana Besser; Benazic, Sasa; Milovanović, Jelena; Jurišević, Milena; Djordjevic, Dragana; Nikolić, Miloš; Mijajlović, Marina; Ratković, Zoran; Radisavljević, Snežana; Petrović, Biljana; Radosavljević, Gordana; Milovanovic, Marija; Arsenijević, Nebojša

doi:10.1007/s11243-018-0260-2

Cited by 6 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Palladium complexes with the same ligands showed a better antitumor effect on human colorectal cancer cells, HCT116 and CaCo-2, and human lung adenocarcinoma, A549, compared with the same copper complexes [53][54][55]. Zn(II) complexes with the same ligands showed relatively moderate cytotoxicity on murine, 4T1, and human, MDA-MB-468, breast carcinoma cells [56]. Platinum(IV) complexes with the same ligands showed significant cytotoxicity on murine leukemia cell, BCL1, and a moderate to weak effect on human B-prolymphocytic leukemia cell, JVM-13 [57].…”

Section: Discussionmentioning

confidence: 95%

Docking Studies, Cytotoxicity Evaluation and Interactions of Binuclear Copper(II) Complexes with S-Isoalkyl Derivatives of Thiosalicylic Acid with Some Relevant Biomolecules

Dimitrijević,

Solovjova,

Bukonjić

et al. 2023

IJMS

View full text Add to dashboard Cite

The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5′-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.

show abstract

Section: Discussionmentioning

confidence: 95%

Docking Studies, Cytotoxicity Evaluation and Interactions of Binuclear Copper(II) Complexes with S-Isoalkyl Derivatives of Thiosalicylic Acid with Some Relevant Biomolecules

Dimitrijević,

Solovjova,

Bukonjić

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Since Pt( S -pr-thiosal)2 complex has previously shown the strongest cytotoxic effect on murine CLL cells, BCL1 [ 22 ], the potential of this complex to induce BCL1 cell apoptosis was analyzed. Flow cytometry analysis of Annexin V and propidium iodide-stained BCL1 cells 24 h after treatment with Pt( S -pr-thiosal)2, in two different doses of 0.1 mg/mL and 0.05 mg/mL revealed that the tested complex induced apoptosis of BCL1 cells ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Modification of salicylates [ 19 ] and conjugation of modified salicylates with different metals [ 20 , 21 ] resulted in compounds with stronger antitumor activity. We have previously synthesized and characterized platinum(IV) complexes with S-alkyl derivatives of thiosalicylic acid [ 19 ] and we have shown significant cytotoxic activity of these complexes toward murine leukemia lymphoma cell line (BCL1) and human B-prolymphocytic leukemia (JVM-13) [ 22 ]. Others also reported stronger antitumor activity of platinum complexes with non-steroidal anti-inflammatory drugs than cisplatin [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…This complex also decreased the expression of STAT3 in murine breast cancer cells and decreased the expression of STAT3 targeted genes [ 21 ]. The highest cytotoxic potential toward murine B cell leukemia lymphoma cell line, BCL1, showed platinum(IV) complex with S propyl thiosalicylic acid (named Pt( S -pr-thiosal)2 complex), similar to the activity of cisplatin, based on half maximal inhibitory concentration (IC50) values 2.47 ± 0.84 for Pt( S -pr-thiosal)2 versus 2.04 ± 0.79 for cisplatin [ 22 ]. Inhibition of STAT3 phosphorylation by different platinum complexes has been reported previously [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Pt(S-pr-thiosal)2 and BCL1 Leukemia Lymphoma: Antitumor Activity In Vitro and In Vivo

Silconi

Rosic

Benazic

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

B cell malignancies are, despite the development of targeted therapy in a certain percentage of the patients still a chronic disease with relapses, requiring multiple lines of therapy. Regimens that include platinum-based drugs provide high response rates in different B cell lymphomas, high-risk chronic lymphocytic leukemia (CLL), and devastating complication of CLL, Richter’s syndrome. The aim of this study was to explore the potential antitumor activity of previously synthetized platinum(IV) complex with alkyl derivatives of thyosalicilc acid, PtCl2(S-pr-thiosal)2, toward murine BCL1 cells and to delineate possible mechanisms of action. The PtCl2(S-pr-thiosal)2 reduced the viability of BCL1 cells in vitro but also reduced the growth of metastases in the leukemia lymphoma model in BALB/c mice. PtCl2(S-pr-thiosal)2 induced apoptosis, inhibited proliferation of BCL1 cells, and induced cell cycle disturbance. Treatment of BCL1 cells with PtCl2(S-pr-thiosal)2 inhibited expression of cyclin D3 and cyclin E and enhanced expression of cyclin-dependent kinase inhibitors p16, p21, and p27 resulting in cell cycle arrest in the G1 phase, reduced the percentage of BCL1 cells in the S phase, and decreased expression of Ki-67. PtCl2(S-pr-thiosal)2 treatment reduced expression of phosphorylated STAT3 and downstream-regulated molecules associated with cancer stemness and proliferation, NANOG, cyclin D3, and c-Myc, and expression of phosphorylated NFκB in vitro and in vivo. In conclusion, PtCl2(S-pr-thiosal)2 reduces STAT3 and NFκB phosphorylation resulting in inhibition of BCL1 cell proliferation and the triggering of apoptotic cell death.

show abstract

DNA binding and antitumor activities of zinc(II) complexes with some S-alkenyl derivatives of thiosalicylic acid

et al. 2018

View full text Add to dashboard Cite

DNA binding and antitumor activities of platinum(IV) and zinc(II) complexes with some S-alkyl derivatives of thiosalicylic acid

Cited by 6 publications

References 46 publications

Docking Studies, Cytotoxicity Evaluation and Interactions of Binuclear Copper(II) Complexes with S-Isoalkyl Derivatives of Thiosalicylic Acid with Some Relevant Biomolecules

Docking Studies, Cytotoxicity Evaluation and Interactions of Binuclear Copper(II) Complexes with S-Isoalkyl Derivatives of Thiosalicylic Acid with Some Relevant Biomolecules

The Pt(S-pr-thiosal)2 and BCL1 Leukemia Lymphoma: Antitumor Activity In Vitro and In Vivo

DNA binding and antitumor activities of zinc(II) complexes with some S-alkenyl derivatives of thiosalicylic acid

Contact Info

Product

Resources

About