Indium(III) complexes with 2-acetylpyridine-derived thiosemicarbazones exhibit cytotoxic activity against human leukemia and solid tumor cell lines

Oliveira, A.; Perdigão, Gabriele M. C.; Silva, Jéferson G. Da; Souza-Fagundes, Elaine M.; Beraldo, Heloísa

doi:10.1016/j.poly.2017.06.045

Cited by 13 publications

(4 citation statements)

References 26 publications

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“…Metal complexes with thiosemicarbazones also show pharmacological applications as antineoplastic − antimicrobial, antitrypanosomal, , and antiviral agents.…”

Section: Introductionmentioning

confidence: 99%

Triethylphosphinegold(I) Complexes with Secnidazole-Derived Thiosemicarbazones: Cytotoxic Activity against HCT-116 Colorectal Cancer Cells under Hypoxia Conditions

et al. 2020

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Triethylphosphinegold(I) complexes [Au(HL1)P-(CH 2 CH 3 ) 3 ]PF 6 (1), [Au(HL2)P(CH 2 CH 3 ) 3 ]PF 6 (2), and [Au-(HL3)P(CH 2 CH 3 ) 3 ]PF 6 (3) were obtained with (E)-2-(1-(2m e t h y l -5 -All compounds were assayed for their cytotoxic activities against HCT-116 colorectal carcinoma cells under normoxia and hypoxia conditions and against nonmalignant HEK-293 human embryonic kidney cells under normoxia conditions. The thiosemicarbazone ligands HL1-HL3 were inactive against HCT-116 cells under hypoxia but while HL3 was inactive, HL1 and HL2 proved to be cytotoxic to both cell lineages under normoxia conditions. Complexes (1−3) and the triethylphosphinegod(I) precursor proved to be active against both cell lineages in normoxia as well as in hypoxia. While 1 and 3 revealed to be active against HEK-293 and HCT-116 cells, being approximately as active against HCT-116 cells in normoxia as under hypoxia, complex (2) proved to be more active against HCT-116 cells under hypoxia than under normoxia conditions, and more active against HCT-116 cells than against the nonmalignant HEK-293 cells, with the selectivity index, calculated as SI = IC 50HEK-293 /IC 50HCT-116hypoxia , equal to 3.7, similar to the value obtained for the control drug tirapazamine (tirapazamine (TPZ), SI = 4). Although the compounds showed distinct cytotoxic activities, the electrochemical behaviors of HL1-HL3 were very similar, as were the behaviors of complexes (1−3). Complex (2) deserves special interest since it was significantly more active under hypoxia than under normoxia conditions. Hence, in this case, selective reduction of the nitro group in a low oxygen pressure environment, resulting in toxic reactive oxygen species (ROS) and damage to DNA or other biomolecules, might operate, while for the remaining compounds, other modes of action probably occur.

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“…Metal complexes with thiosemicarbazones also show pharmacological applications as antineoplastic − antimicrobial, antitrypanosomal, , and antiviral agents.…”

Section: Introductionmentioning

confidence: 99%

Triethylphosphinegold(I) Complexes with Secnidazole-Derived Thiosemicarbazones: Cytotoxic Activity against HCT-116 Colorectal Cancer Cells under Hypoxia Conditions

et al. 2020

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“…Finally, a Pd(II) complex with a putative composition of [Pd(η 3 -allyl)(N 3 )] was proposed as an intermediate in palladium-catalyzed 1,3-dipolar cycloadditions. − Thus, in order to systematically evaluate the kinetics of the iClick reaction for an isoelectronic and isostructural series of square-planar late transition-metal complexes, we prepared palladium(II) and platinum(II) azido complexes with a N ∧ N ∧ S chelating coligand based on thiosemicarbazone, which also features a methyl group with a distinct chemical shift to serve as a NMR spectroscopic marker in kinetic studies, and studied their reaction with a variety of alkynes. The selection of the thiosemicarbazone coligand was also inspired by the well-established pharmacological activity of the purely organic compound and its metal complexes. − …”

Section: Introductionmentioning

confidence: 99%

iClick Reactions of Square-Planar Palladium(II) and Platinum(II) Azido Complexes with Electron-Poor Alkynes: Metal-Dependent Preference for N1 vs N2 Triazolate Coordination and Kinetic Studies with ¹H and ¹⁹F NMR Spectroscopy

et al. 2019

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Two square-planar palladium(II) and platinum(II) azido complexes [M(N 3 )(L)] with L = N-phenyl-2-[1-(2-pyridinyl)ethylidene]hydrazine carbothioamide reacted with four different electron-poor alkynes R−CC−R′ with R = R′ = COOCH 3 , COOEt, COOCH 2 CH 2 OCH 3 or R = CF 3 , R′ = COOEt in a [3 + 2] cycloaddition "iClick" reaction. The resulting triazolate complexes [M-(triazolate R,R' )(L)] were isolated by simple precipitation and/or washing in high purity and good yield. Six out of the eight new compounds feature the triazolate ligand coordinated to the metal center via the N2 nitrogen atom, but fortuitous solubility properties allowed isolation of the N1 isomer in two cases from acetone. When the solvent was changed to DMSO, the N1 → N2 isomerization could be studied by NMR spectroscopy and took several days to complete. 19 F NMR studies of the iClick reaction with F 3 C−CC−COOEt led to identification of a putative early linear intermediate in addition to the N1 and N2 isomers, however with the latter as the final product. Rate constants determined by 1 H or 19 F NMR spectroscopy increased in the order Pd > Pt and CF 3 /COOEt > COOR/COOR with R = CH 3 , Et, CH 2 CH 2 OCH 3 . The second-order rate constant k 2 > 3.7 M −1 s −1 determined for the reaction of [Pd(N 3 )(L)] with F 3 C− CC−COOEt is the fastest observed for an iClick reaction so far and compares favorably with that of the most evolved strained alkynes reported for the SPAAC (strain-promoted azide−alkyne cycloaddition) to date. Selected title compounds were evaluated for their anticancer activity on the GaMG human glioblastoma brain cancer cell line and gave EC 50 values in the low micromolar range (2−16 μM). The potency of the Pd(II) complexes increased with the chain length of the substituents in the 4-and 5-positions of the triazolate ligand.

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“…Thiosemicarbazones have been extensively studied in the past several decades because of their three main advantages: (1) thiosemicarbazones are novel and promising anticancer agents; , (2) the anticancer activity of thiosemicarbazones can be regulated by aldehydes and ketones with different structures reacting with thiosemicarbazide or replacing the hydrogen atom(s) in the N-position of thiosemicarbazones with different functional group(s); , and (3) thiosemicarbazones are excellent metal-chelating agents because of their N,N,S-donor ligand set. , At present, rationally combining the properties of the metal ion and the active compound has been a promising approach to the design of anticancer metal agents. Indeed, metal thiosemicarbazone compounds have also been extensively studied and have been found to be one of the most promising next-generation metal anticancer agents because they can inhibit tumor growth by multiple mechanisms. − Currently, In compounds are used in antitumor research owing to the following advantages: (1) In 3+ presents affinity for nitrogen and oxygen donor ligands and can form stable compounds with phenol, carboxylate, and amine ligands, as well as with sulfur-containing groups; , (2) In(III) compounds with ligands significantly increased antitumor activity relative to the ligands alone; − and (3) the affinity of In compounds to transferrin might favor targeting of In(III) compounds to tumor cells, improving the selectivity . Excitingly, several In thiosemicarbazone compounds have also been synthesized and have shown remarkable antitumor activity. − However, there still remain mysteries about their antitumor function and mechanism, including the ability and mechanism of In compounds to overcome cisplatin resistance.…”

Section: Introductionmentioning

confidence: 99%

Developing a Novel Indium(III) Agent Based on Liposomes to Overcome Cisplatin-Induced Resistance in Breast Cancer by Multitargeting the Tumor Microenvironment Components

et al. 2021

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To overcome the resistance of cancer cells to platinumbased drugs and effectively suppress tumor growth, we developed a novel indium (In) agent based on liposomes (Lips). Thus, we not only obtained an In(III) thiosemicarbazone agent (5b) with remarkable cytotoxicity by optimizing a series of In(III) thiosemicarbazone agents (1b−5b) but also successfully constructed a novel 5b-loaded Lip (5b-Lip) delivery system. Importantly, in vitro and in vivo results revealed that 5b/5b-Lip overcame the tumor cell resistance and effectively inhibited MCF-7/DDP tumor growth. In addition, Lips improved the intracellular accumulation of 5b. We also confirmed the mechanism by which 5b/5b-Lip overcomes breast cancer cell resistance. 5b/5b-Lip cannot act against DNA in cancer cells but attacks the two cell components in the tumor microenvironment, namely, by inducing apoptosis and lethal autophagy of cancer cells and resetting tumor-promoting M2 macrophages to the tumor-killing M1 phenotype.

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Indium(III) complexes with 2-acetylpyridine-derived thiosemicarbazones exhibit cytotoxic activity against human leukemia and solid tumor cell lines

Cited by 13 publications

References 26 publications

Triethylphosphinegold(I) Complexes with Secnidazole-Derived Thiosemicarbazones: Cytotoxic Activity against HCT-116 Colorectal Cancer Cells under Hypoxia Conditions

Triethylphosphinegold(I) Complexes with Secnidazole-Derived Thiosemicarbazones: Cytotoxic Activity against HCT-116 Colorectal Cancer Cells under Hypoxia Conditions

iClick Reactions of Square-Planar Palladium(II) and Platinum(II) Azido Complexes with Electron-Poor Alkynes: Metal-Dependent Preference for N1 vs N2 Triazolate Coordination and Kinetic Studies with ¹H and ¹⁹F NMR Spectroscopy

Developing a Novel Indium(III) Agent Based on Liposomes to Overcome Cisplatin-Induced Resistance in Breast Cancer by Multitargeting the Tumor Microenvironment Components

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Indium(III) complexes with 2-acetylpyridine-derived thiosemicarbazones exhibit cytotoxic activity against human leukemia and solid tumor cell lines

Cited by 13 publications

References 26 publications

Triethylphosphinegold(I) Complexes with Secnidazole-Derived Thiosemicarbazones: Cytotoxic Activity against HCT-116 Colorectal Cancer Cells under Hypoxia Conditions

Triethylphosphinegold(I) Complexes with Secnidazole-Derived Thiosemicarbazones: Cytotoxic Activity against HCT-116 Colorectal Cancer Cells under Hypoxia Conditions

iClick Reactions of Square-Planar Palladium(II) and Platinum(II) Azido Complexes with Electron-Poor Alkynes: Metal-Dependent Preference for N1 vs N2 Triazolate Coordination and Kinetic Studies with 1H and 19F NMR Spectroscopy

Developing a Novel Indium(III) Agent Based on Liposomes to Overcome Cisplatin-Induced Resistance in Breast Cancer by Multitargeting the Tumor Microenvironment Components

Contact Info

Product

Resources

About

iClick Reactions of Square-Planar Palladium(II) and Platinum(II) Azido Complexes with Electron-Poor Alkynes: Metal-Dependent Preference for N1 vs N2 Triazolate Coordination and Kinetic Studies with ¹H and ¹⁹F NMR Spectroscopy