Investigation of in vitro anticancer and DNA strap interactions in live cells using carboplatin type Cu(II) and Zn(II) metalloinsertors

Pravin, Narayanaperumal; Raman, Natarajan

doi:10.1016/j.ejmech.2014.08.036

Cited by 41 publications

(15 citation statements)

References 42 publications

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“…Metalloinserters and metallointercalators exploit noncovalent interactions of planar aromatic ligands to inhibit DNA repair because they show unwinding of DNA to π-stack between base pairs, groove binding, or insertion into a destabilized site (12,13). Covalent interactions can be used to directly bind complexes to the DNA duplex whereas the ligands may be functionalized for subsequent reactions such as radicalinduced DNA cleavage (14)(15)(16)(17)(18)(19). Complexes using these mechanisms often demonstrate inhibition of DNA replication, leading to G2 arrest to halt progression of the damaged DNA during the cell cycle; however, many suffer from lengthy reaction times of up to 48 h or inefficient DNA degradation.…”

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confidence: 99%

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Porter

Lindahl

Lietzke

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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) for Cu(PyED)·2Cl, indicating three nitrogens and a chloride in the psuedo-equatorial plane with the remaining pyridine nitrogen and solvent in axial positions. EPR spectra of the Cu(II) complexes exhibit an axially elongated octahedron. This spectroscopic evidence, together with density functional theory computed geometries, suggest six-coordinate structures for Cu(II) and Fe(II) complexes and a five-coordinate environment for Zn(II) analogs. Bergman cyclization via thermal activation of these constructs yields benzannulated product indicative of diradical generation in all complexes within 3 h at 37°C. A significant metal dependence on the rate of the reaction is observed [Cu(II) > Fe(II) > Zn(II)], which is mirrored in in vitro DNA-damaging outcomes. Whereas in situ chelation of PyED leads to considerable degradation in the presence of all metals within 1 h under hyperthermia conditions, Cu(II) activation produces >50% compromised DNA within 5 min. Additionally, Cu(II) chelated PyED outcompetes DNA polymerase I to successfully inhibit template strand extension. Exposure of HeLa cells to Cu(PyBD)·SO 4 (IC 50 = 10 μM) results in a G2/M arrest compared with untreated samples, indicating significant DNA damage. These results demonstrate metal-controlled radical generation for degradation of biopolymers under physiologically relevant temperatures on short timescales. metal-mediated radicals | DNA degradation | polymerase inhibition | enediyne | Bergman cyclization

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confidence: 99%

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Porter

Lindahl

Lietzke

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…It is noteworthy that the obtained products constitutea ni mportant class of building block for the synthesis of biologically and pharmaceutically relevant compounds. [33] For other enol carboxylates such as ethyl 3-acetyloxy-3-(phenyl)prop-2-enoate (5d;R 1 = C 6 H 5 ,R 2 = OEt, R 3 = Me) and 3-acetyloxy-3-(4-mehoxyphenyl)prop-2-enoate( 5e;R 1 = 4-MeOC 6 H 4 , R 2 = OEt, R 3 = Me), the reaction also proceed smoothly providing products 6a-f with the yields up to 72 % ( Figure 3). Electron-rich aldehydes gave higher yields than their electron-deficient counterparts.…”

Section: Resultsmentioning

confidence: 99%

Enzyme Promiscuity as a Remedy for the Common Problems with Knoevenagel Condensation

Koszelewski

Ostaszewski

2019

Chemistry A European J

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A new protocol based on lipase‐catalyzed tandem reaction toward α,β‐enones/enoesters is presented. For the synthesis of the desired products the tandem process based on enzyme‐catalyzed hydrolysis and Knoevenagel reaction starting from enol acetates and aldehyde is developed. The relevant impact of the reaction conditions including organic solvent, enzyme type, and temperature on the course of the reaction was revealed. It was shown that controllable release of the active methylene compound from the corresponding enol carboxylate ensured by enzymatic reaction diminishes significantly the formation of the unwanted co‐products. Furthermore, this protocol was extended by including a second tandem chemoenzymatic transformation engaging various aldehyde precursors. After a careful optimization of the reaction conditions, the target products were obtained with yields up to 86 % and with excellent E/Z‐selectivity.

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“…Based on the abovementioned results, we hypothesized that Zn(TAC) would have stronger tumor growth inhibition (TGI, %) compared with an equivalent treatment regimen with Zn(TA) and the clinical drug cisplatin. To test this, we used a human-relevant lung pneumocyte cancer cell line for treatment with Zn(TA) and Zn(TAC) via intraperitoneal injection 93–100 as well as an A549/DDP cell line xenograft model. Tumor regression (TGI = 57.4%) was observed in the A549/DDP xenograft model with Zn(TAC) after an intraperitoneal injection of Zn(TA) (2.0 mg kg −1 ) or Zn(TAC) (2.0 mg kg −1 ) every 2 days (q2d) for 15 days (Fig.…”

Section: Resultsmentioning

confidence: 99%

Complexes of Zn(ii) with a mixed tryptanthrin derivative and curcumin chelating ligands as new promising anticancer agents

Wang

Nong

et al. 2022

Dalton Trans.

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Investigation of in vitro anticancer and DNA strap interactions in live cells using carboplatin type Cu(II) and Zn(II) metalloinsertors

Cited by 41 publications

References 42 publications

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Enzyme Promiscuity as a Remedy for the Common Problems with Knoevenagel Condensation

Complexes of Zn(ii) with a mixed tryptanthrin derivative and curcumin chelating ligands as new promising anticancer agents

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