Gold(I) complexes with aryl-thiosemicarbazones: Molecular modeling, synthesis, cytotoxicity and TrxR inhibition

Tavares, Tatiane Teixeira; Azevedo, Gustavo Chevitarese; García, Adrián Luis García; Carpanez, Arthur G.; Lewer, Pâmela Matos; Paschoal, Diego; Müller, Bruno L.; Santos, Hélio F. Dos; Matos, Renato Camargo; Silva, Heveline; Grazul, Richard Michael; Fontes, Ana Paula Soares

doi:10.1016/j.poly.2017.05.004

Cited by 31 publications

(25 citation statements)

References 67 publications

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“…e antiproliferative activity of the thiosemicarbazones derivatives and 5-fluorouracile is shown in Table 3. ese results allow to confirm that the cytotoxic activity is enhanced when the OCH 2 CF 3 substituent group is bound in the C-6 position of the pyridine ring [44]. As compared to the 5-fluorouracile (5-FU) anticancer agent (IC 50 = 7.51 μM), 1 exhibited a higher cytotoxic effect at low micromolar concentration (IC 50 = 3.6 μM) against the amelanotic melanoma cell line (M-14).…”

Section: Antitumor Evaluationmentioning

confidence: 69%

Section: Antitumor Evaluationmentioning

confidence: 99%

“…Compound 1 tested in vitro against the amelanotic melanoma cell line (M-14) (IC 50 = 3.36 μM) showed to be more cytotoxic as compared to pyridine-2-carbaldehyde thiosemicarbazone (IC 50 => 100 μM) assayed in vitro against the mouse metastatic skin melanoma (B16F10) cell line [44]. Nevertheless, 1 (IC 50 = 11.25 μM) tested in vitro against the colon adenocarcinoma (HT-29) was slightly less active than pyridine-2-carbaldehyde thiosemicarbazone (IC 50 = 8.6 μM) and 2-acetylpyridine-N(4)-orthochlorophenyl thiosemicarbazone (IC 50 = 6.96 μM) assayed in vitro against the colon cancer (CT26.WT) and HT-29 cell lines, respectively [44,45]. On the other hand, 3-aminepyridinecarbaldehyde thiosemicarbazone and 3-phenyl-1-pyridin-2-ylprop-2-en-1one thiosemicarbazone tested in vitro against the large cell lung cancer (NCI-H460) [46] and the human breast carcinoma (MDA-MB 231) cell line [10], respectively, were found to be about two times more cytotoxic than 1 tested in vitro against the H460 and MCF-7 cell lines with IC 50 values of 10.9 and 6.27 μM, respectively.…”

Section: Antitumor Evaluationmentioning

confidence: 99%

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Synthesis, Spectroscopic Characterization, Structural Studies, and In Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Hernández

Carrasco

Vaisberg

et al. 2020

Journal of Chemistry

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Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4′-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3′,4′-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3′,5′-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (1H, 13C, 19F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by 1H NMR spectroscopy. The in vitro antitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC50 and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC50 = 3.36 to 21.35 μM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to >582.26 μM) against different types of human tumor cell lines. 1 was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells.

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Section: Antitumor Evaluationmentioning

confidence: 69%

Section: Antitumor Evaluationmentioning

confidence: 99%

Section: Antitumor Evaluationmentioning

confidence: 99%

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Synthesis, Spectroscopic Characterization, Structural Studies, and In Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Hernández

Carrasco

Vaisberg

et al. 2020

Journal of Chemistry

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“…Aryl-thiosemicarbazones have also been described as molecules with biological properties such as nematocidal, insecticidal, antibacterial, antifungal, antiviral, and anti-inflammatory activities. Coordination to gold(I) (complexes 62a–f, Figure 4) [88] did not improve their anticancer activity in murine colon cancer CT26-WT cells; however, the presence of AuPPh 3 units, as in complexes 63a–f, led to a slight improvement and inhibition of the TrxR activity. Drug-receptor docking analysis pointed to the occurrence of binding with Y116 and E30 residues, with Y116 being directly implicated in the enzyme catalysis.…”

Section: Gold(i) Complexesmentioning

confidence: 99%

Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment

Mármol

Medina-Quero

Rodríguez-Yoldi

et al. 2019

Cancers

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Due to the increasing incidence and high mortality associated with colorectal cancer (CRC), novel therapeutic strategies are urgently needed. Classic chemotherapy against CRC is based on oxaliplatin and other cisplatin analogues; however, platinum-based therapy lacks selectivity to cancer cells and leads to deleterious side effects. In addition, tumor resistance to oxaliplatin is related to chemotherapy failure. Gold(I) derivatives are a promising alternative to platinum complexes, since instead of interacting with DNA, they target proteins overexpressed on tumor cells, thus leading to less side effects than, but a comparable antitumor effect to, platinum derivatives. Moreover, given the huge potential of gold nanoparticles, the role of gold in CRC chemotherapy is not limited to gold(I) complexes. Gold nanoparticles have been found to be able to overcome multidrug resistance along with reduced side effects due to a more efficient uptake of classic drugs. Moreover, the use of gold nanoparticles has enhanced the effect of traditional therapies such as radiotherapy, photothermal therapy, or photodynamic therapy, and has displayed a potential role in diagnosis as a consequence of their optic properties. Herein, we have reviewed the most recent advances in the use of gold(I) derivatives and gold nanoparticles in CRC therapy.

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“…The varied chemical as well as biological properties of metal complexes comprising of thiosemicarbazones ligands have attracted researchers for number of years . Heterocyclic compounds when condensed to thiosemicarbazide display biological activities viz .…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Characterization and Biological Evaluation of Ruthenium Complexes of Flavonethiosemicarbazones as Antiproliferative and Mycobacterial Activities

et al. 2018

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The ruthenium(II) complexes of 3-hydroxy-4'-substituted flavonethiosemicarbazones, (where 4'-substituents are -OCH 3 (LB1), -Cl (LB2), NMe 2 (LB3)) with Ru(bpy) 2 Cl 2 and Ru (phen) 2 Cl 2 (bpy = 2, 2' bipyridine; Phen = 1, 10 phenanthroline) viz. [Ru (bpy) were synthesized in good yield. All the compounds were characterized by elemental analysis, IR, 1 H NMR, UV/Vis spectroscopy and ESI-MS. The spectral features of the complexes matches well to their corresponding formula. The gas phase molecular struc-tures of all complexes were determined using density functional theory (DFT) calculations. All the compounds were screened on A549 (Human Lung carcinoma) cell line using the MTT cell viability assay. The anti-mycobacterial drug susceptibility testing (DST) was performed using Resazurin Microtiter plate assay with glycerol as carbon source. The effect of compounds on morphological changes of cultured cells was analysed. The compound MB2 showed good cytotoxic activity against human lung carcinoma cell line A549. Similarly, compound MP2 showed good anti-mycobacterial activity with more than 40% inhibition of growth. Results and Discussion Synthetic aspectsThe ruthenium(II) complexes comprising of 3-hydroxy-4'-substituted flavone thiosemicarbazones ligands and bpy or phen [a] Dr.

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Gold(I) complexes with aryl-thiosemicarbazones: Molecular modeling, synthesis, cytotoxicity and TrxR inhibition

Cited by 31 publications

References 67 publications

Synthesis, Spectroscopic Characterization, Structural Studies, and In Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Synthesis, Spectroscopic Characterization, Structural Studies, and In Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment

Design, Synthesis, Characterization and Biological Evaluation of Ruthenium Complexes of Flavonethiosemicarbazones as Antiproliferative and Mycobacterial Activities

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