Hydrolysis mechanism of (N, N) chelated cytotoxic Pt/Pd(II)-dichloro complexes: A theoretical approach

Mukherjee, Subhajit; Reddy, P B Venkata; Mitra, Ishani; Linert, Wolfgang; Moi, Sankar Ch.

doi:10.1016/j.cplett.2017.04.069

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…The absence of negative frequency eigen values indicate that the optimised structure for all the complexes, shown in Figure are in true minima on global potential energy surface. We have already reported the optimised structure and its parameters for C1 and C2 , where the hydrolysis mechanism of C1 had been investigated. Here, all the corresponding structural parameters for C3 ‐ C6 are summarised in Table which are in well agreement with the literature data for previously reported Pd(II) complexes .…”

Section: Resultsmentioning

confidence: 99%

In Vitro DNA/BSA Binding, Anticancer and Normal Cell Activity of Pd(II) Complexes: Substitution Behaviour and Computational Study

et al. 2018

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In the aspect of an effective palladium based anticancer drug design, Pd(II) complexes [Pd(MAMP)Cl2], C1; [Pd(MAMP)(H2O)2]x2, C2; [Pd(MAMP)(L‐cys)]x, C3; [Pd(MAMP)(N‐ac‐L‐cys)], C4; [Pd(MAMP)(DL‐meth)]x2, C5; and [Pd(MAMP)(DL‐pen)]x, C6 (where x=ClO4−/NO3−) have been synthesised and characterised where 2‐[(methylamino)methyl]pyridine (MAMP) has been considered as carrier ligand and chloride, aqua, L‐cysteine (L‐cys), N‐acetyl‐L‐cysteine (N‐ac‐L‐cys), DL‐methionine (DL‐meth) and DL‐penicillamine (DL‐pen) are selected as leaving group. DNA as well as protein binding ability of the complexes has been investigated with CT‐DNA and BSA and the related binding parameters have been evaluated. Kinetic investigation for the reactions of Pd(II)‐diaqua complex C2 with four selected sulfur containing bio‐molecules have been carried out under pseudo first order condition. In addition, theoretical investigation has also been considered for structural optimisation, frontier molecular orbital mapping, TD‐DFT and NBO analysis. To get an insight into the cytotoxicity, the complexes have been treated on three different cancer cell lines (A549, HeLa, Hep G2) which reveal comparable anticancer activity of the reported complexes with the clinically acquainted anticancer drug Cisplatin. Very less complex initiated reactive oxygen species (ROS) with low degree of cell death in two different non‐tumour cell lines (L6 myotubes and HEK 293) indicate minimum normal cell toxicity of the complexes.

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Section: Resultsmentioning

confidence: 99%

In Vitro DNA/BSA Binding, Anticancer and Normal Cell Activity of Pd(II) Complexes: Substitution Behaviour and Computational Study

et al. 2018

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“…To understand the molecular factors at play in such unique biological action, several theoretical studies focused on bifunctional − and monofunctional − Pt(II) complexes have been carried out. Nevertheless, as far as PtPPH is concerned, the mechanism of action is still under debate.…”

Section: Introductionmentioning

confidence: 99%

Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action

Veclani

Tolazzi

Cerón‐Carrasco

et al. 2021

J. Chem. Inf. Model.

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Phenanthriplatin (PtPPH) is a monovalent platinum(II)-based complex with a large cytotoxicity against cancer cells. Although the aqua-activated drug has been assumed to be the precursor for DNA damage, it is still under debate whether the way in which that metallodrug attacks to DNA is dominated by a direct binding to a guanine base or rather by an intercalated intermediate product. Aiming to capture the mechanism of action of PtPPH, the present contribution used theoretical tools to systematically assess the sequence of all possible mechanisms on drug activation and reactivity, for example, hydrolysis, intercalation, and covalent damage to DNA. Ab initio quantum mechanical (QM) methods, hybrid QM/QM′ schemes, and independent gradient model approaches are implemented in an unbiased protocol. The performed simulations show that the cascade of reactions is articulated in three well-defined stages: (i) an early and fast intercalation of the complex between the DNA bases, (ii) a subsequent hydrolysis reaction that leads to the aqua-activated form, and (iii) a final formation of the covalent bond between PtPPH and DNA at a guanine site. The permanent damage to DNA is consequently driven by that latter bond to DNA but with a simultaneous π–π intercalation of the phenanthridine into nucleobases. The impact of the DNA sequence and the lateral backbone was also discussed to provide a more complete picture of the forces that anchor the drug into the double helix.

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Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential

Leal

Santos

Fernández-Aroca

et al. 2021

Journal of Inorganic Biochemistry

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Hydrolysis mechanism of (N, N) chelated cytotoxic Pt/Pd(II)-dichloro complexes: A theoretical approach

Cited by 4 publications

References 36 publications

In Vitro DNA/BSA Binding, Anticancer and Normal Cell Activity of Pd(II) Complexes: Substitution Behaviour and Computational Study

In Vitro DNA/BSA Binding, Anticancer and Normal Cell Activity of Pd(II) Complexes: Substitution Behaviour and Computational Study

Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action

Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential

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