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Water-Soluble Chalcogenide W₆-Clusters: On the Way to Biomedical Applications.

ABSTRACT: Despite the great potential of octahedral tungsten cluster complexes in fields of biomedical applications such as X-ray computed tomography or angiography, there is only one example of a water-soluble W₆Q₈-cluster that has been reported in the literature. Herein we present the synthesis and a detailed characterization including X-ray structural analysis, NMR, IR, UV-Vis spectroscopies, HR-MS spectrometry, and the electrochemical behavior of two new cluster complexes of the general formula W₆Q₈L₆ with phosphine ligands containing a hydrophilic carboxylic group, which makes the complexes soluble in an aqueous medium. The hydrolytic stability of the clusters' aqueous solutions allows us to investigate for the first time the influence of W₆-clusters on cell viability. The results obtained clearly demonstrate their very low cytotoxicity, comparable to the least-toxic clusters presented in the literature.

SUBMITTER: Gassan AD

PROVIDER: S-EPMC9369320 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Water-Soluble Chalcogenide W6-Clusters: On the Way to Biomedical Applications.

Gassan Alena D AD Ivanov Anton A AA Pozmogova Tatiana N TN Eltsov Ilia V IV Kuratieva Natalia V NV Mironov Yuri V YV Shestopalov Michael A MA

International journal of molecular sciences 20220805 15

Despite the great potential of octahedral tungsten cluster complexes in fields of biomedical applications such as X-ray computed tomography or angiography, there is only one example of a water-soluble W6Q8-cluster that has been reported in the literature. Herein we present the synthesis and a detailed characterization including X-ray structural analysis, NMR, IR, UV-Vis spectroscopies, HR-MS spectrometry, and the electrochemical behavior of two new cluster complexes of the ...[more]

PMID: 35955875

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Project description:Mostotrin (MT), a novel compound, at least five orders of magnitude more soluble in water than its mother substance, was designed and synthesised from tryptanthrin (TR). Its structure was established by nuclear magnetic resonance and mass spectrometry data and confirmed by X‑ray analysis, revealing that MT is a pentacyclic product with an additional pseudo‑cycle formed with the participation of one intramolecular hydrogen bond. Antimicrobial activity and cytotoxic action against tumour cells in vitro, as well as anti‑tumour effects, acute toxicity and anti‑inflammatory activities in vivo, were evaluated. Antimicrobial properties of MT against Mycobacterium spp and Bacillus cereus ATCC 10702 appeared to be the same as that of TR, but against the other strains used it was weaker. Furthermore, MT exhibited 5‑10 times higher cytotoxic activities against tumour cell lines HCT‑116, МСF‑7 and K‑562 than TR, but was less toxic than TR (LD50 of MT was 375 mg/kg, while LD50 for TR was 75 mg/kg). Additionally, compounds MT and TR were studied in DNA binding tests. The quenching of its fluorescence on addition to DNA solution established MT to be capable of binding to DNA. Its anti‑tumour action in vivo on mice with the ascitic form of Ehrlich carcinoma was promising, particularly with joint application of MT and the antitumour drug doxorubicin. In this model, the survival and life span for the doxorubicin and 1 co‑treatment group were significantly higher compared to doxorubicin treatment alone. The compound MT showed a lower immunosuppressive effect than TR at the early stages of inflammation induced in mice by LPS from E. сoli (MT hardly inhibited the release of IL‑1, IL‑2, or INF‑γ). These results demonstrated that MT is a perspective hit compound for drug development. In our opinion, further evaluation on the biological effects of MT and its synthetic analogues could lead to safer and more effective anti‑tumour and anti‑tuberculosis agents than TR itself. MT has also the prospect of application in combination with known anti‑tumour drugs for the treatment of oncological diseases.

Dataset Information

Water-Soluble Chalcogenide W₆-Clusters: On the Way to Biomedical Applications.

Publications

Water-Soluble Chalcogenide W<sub>6</sub>-Clusters: On the Way to Biomedical Applications.

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