Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA

Various Pt IV diazides have been investigated over the years as light-activatable prodrugs that interfere with cell proliferation, accumulate in cancer cells and cause cell death. The potencies of the complexes vary depending on the substituted amines (pyridine=piperidine>ammine) as well as the coordination geometry ( trans diazide> cis ). Light-activated Pt IV diazides tend to be less specific than cisplatin at inhibiting cancer cell growth, but cells resistant to cisplatin show little cross-resistance to Pt IV diazides. Platinum is accumulated in the cancer cells to a similar level as cisplatin, but only when activated by light, indicating that reactive Pt species form photolytically. Studies show that Pt also becomes attached to cellular DNA upon the light activation of various Pt IV diazides. Structures of some of the photolysis products were elucidated by LC–MS/MS; monoaqua- and diaqua-Pt II complexes form that are reactive towards biomolecules such as calf thymus DNA. Platination of calf thymus DNA can be blocked by the addition of nucleophiles such as glutathione and chloride, further evidence that aqua-Pt II species form upon irradiation. Evidence is presented that reactive oxygen species may be generated in the first hours following photoactivation. Cell death does not take the usual apoptotic pathways seen with cisplatin, but appears to involve autophagy. Thus, photoactivated diazido-Pt IV complexes represent an interesting class of potential anti-cancer agents that can be selectively activated by light and kill cells by a mechanism different to the anti-cancer drug cisplatin.

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Molecular recognition of synthesized halogenated chalcone by calf thymus DNA through multispectroscopic studies and analysis the anti-cancer, anti-bacterial activity of the compounds

Journal of Molecular Liquids ◽

10.1016/j.molliq.2021.116504 ◽

2021 ◽

pp. 116504

Author(s):

Abhijit Mukherjee ◽

Suvranil Ghosh ◽

Sudipta Ghosh ◽

Sachinta Mahato ◽

Mahadeb Pal ◽

...

Keyword(s):

Molecular Recognition ◽

Bacterial Activity ◽

Calf Thymus Dna ◽

Calf Thymus ◽

Anti Cancer

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DNA-binding, photocleavage and anti-cancer activity of tin(IV) corrole

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424618500256 ◽

2018 ◽

Vol 22 (09n10) ◽

pp. 739-750 ◽

Cited By ~ 6

Author(s):

An-Na Xie ◽

Zhao Zhang ◽

Hua-Hua Wang ◽

Atif Ali ◽

Dong-Xu Zhang ◽

...

Keyword(s):

Dna Binding ◽

Binding Mode ◽

Calf Thymus Dna ◽

Free Base ◽

Docking Analysis ◽

Calf Thymus ◽

Anti Cancer ◽

Active Intermediate ◽

Dna Scission ◽

Cancer Activity

A new tin(IV) corrole, 5,10,15-tris(4-methoxycarbonylphenyl) corrole tin(IV) (1-Sn) was synthesized and characterized. The DNA binding, photocleavage and anti-cancer activity were studied and compared with its free-base. The interaction of 1-Sn and its free-base 1 with calf thymus DNA had been investigated by spectroscopic methods, viscosity measurements and molecular docking analysis. The results revealed that 1-Sn and 1 could interact with calf thymus DNA via an outside groove binding mode. Furthermore, although 1 displayed no photonuclease activity, 1-Sn exhibited good photonuclease activity as indicated by agarose gel electrophoresis, and superoxide anion might be the active intermediate for the DNA scission. Finally, 1 was nontoxic but 1-Sn displayed cytotoxicity towards A549 tumor cell lines.

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