Multi-target compounds acting in cancer progression: Focus on thiosemicarbazone, thiazole and thiazolidinone analogues

Siqueira, Lucianna Râbelo Pessôa de; Gomes, Paulo André Teixeira de Moraes; Ferreira, Larissa Pelágia de Lima; Rêgo, Moacyr Jesus Barreto de Melo; Leite, Ana Cristina Lima

doi:10.1016/j.ejmech.2019.03.024

Cited by 109 publications

(47 citation statements)

References 85 publications

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“…Thiosemicarbazones (TSCs) and their metal complexes are versatile molecules with a wide spectrum of antimicrobial, antitrypanosomal, antitumor, antimalarial, and antiviral activities and have been studied intensely in pharmaceutical and medicinal chemistry [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. TSCs are able to block the genetic expression of wide variety of viruses [ 11 , 13 ], including the herpes simplex virus [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization and Release Behavior of a Thiosemicarbazone from Electrospun Polyvinyl Alcohol Core-Shell Nanofibers

et al. 2020

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Mats of polyvinyl alcohol (PVA) core–shell nanofibers were produced using coaxial electrospinning in the presence of a thiosemicarbazone (TSC) N4-(S)-1-phenylethyl)-2-(pyridin-2-yl-ethylidene)hydrazine-1-carbothioamide (HapyTSCmB). Monolithic fibers with 0% or 5% TSC and core–shell fibers with 10% TSC in the spinning solution were studied to compare stability and release rates. SEM showed the formation of uniform, bead-free, cylindrical, and smooth fibers. NMR spectroscopy and thermal analysis (TG/DTA) gave proof for the chemical integrity of the TSC in the fiber mats after the electrospinning process. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy showed no TSC on the surface of the PVA/TSC-PVA fibers confirming the core–shell character. The TSC release profiles of the fibers as studied using UV-vis absorption spectroscopy showed a slower release from the PVA/TSC-PVA core–shell structure compared with the monolithic PVA/TSC fibers as well as lower cumulative release percentage (17%). Out of several release models, the Korsmeyer–Peppas model gave the best fit to the experimental data. The main release phase can be described with a Fick-type diffusion mechanism. Antibacterial properties were tested against the Gram-positive Staphylococcus aureus bacterium and gave a minimal inhibitory concentration of 12.5 μg/mL. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT)-based cytotoxicity experiments showed that the cell viability of fibroblast at different contents of TSC was slightly decreased from 1.5% up to 3.5% when compared to control cells.

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Section: Introductionmentioning

confidence: 99%

Characterization and Release Behavior of a Thiosemicarbazone from Electrospun Polyvinyl Alcohol Core-Shell Nanofibers

et al. 2020

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“…All samples for NMR measurements were prepared by dissolving the compounds in [D 6 ]DMSO. 1 H, 13 C, COSY, HSQC, HMBC NMR spectra were acquired on a Bruker Avance III 500 MHz FT NMR spectrometer at NMR spectrometry Centre of the Faculty of Chemistry of the University of Vienna. 1 H and 13 C NMR shifts were referred relative to residual solvent signal.…”

Section: Chemicalsmentioning

confidence: 99%

“…The first compound was tested in vivo in the 1950s, attracting the interest of researchers [1]. Since then, a large number of TSCs with antiproliferative activity has been reported, but only some of them reached clinical trials [2].The academic interest in TSCs has been recently rekindled, when two new compounds, namely COTI-2 ((E)-N -(5,6,7,8-tetrahydroquinolin-8-ylidene)-4-(pyridine-2-yl)piperazine-1-carbothiohydrazide) and DpC (di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone), entered phase I clinical trials for the treatment of gynaecological malignancies, colorectal, lung, pancreatic cancer and advanced (or resistant) tumours [3,4].TSCs and their metal complexes are intracellularly reactive agents with multi-target features [5][6][7][8][9][10][11][12][13][14], which often exhibit marked cytotoxic effects both in vitro and in vivo, as described elsewhere [1,2,15,16]. The aromatic moiety and metal-binding domain are the basic structural requisites for their pharmacological activity.…”

Section: Introductionmentioning

confidence: 99%

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Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters

et al. 2020

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A series of four water-soluble salicylaldehyde thiosemicarbazones with a positively charged trimethylammonium moiety ([H2LR]Cl, R = H, Me, Et, Ph) and four copper(II) complexes [Cu(HLR)Cl]Cl (1–4) were synthesised with the aim to study (i) their antiproliferative activity in cancer cells and, (ii) for the first time for thiosemicarbazones, the interaction with membrane transport proteins, specifically organic cation transporters OCT1–3. The compounds were comprehensively characterised by analytical, spectroscopic and X-ray diffraction methods. The highest cytotoxic effect was observed in the neuroblastoma cell line SH-5YSY after 24 h exposure and follows the rank order: 3 > 2 > 4 > cisplatin > 1 >>[H2LR]Cl. The copper(II) complexes showed marked interaction with OCT1–3, comparable to that of well-known OCT inhibitors (decynium 22, prazosin and corticosterone) in the cell-based radiotracer uptake assays. The work paves the way for the development of more potent and selective anticancer drugs and/or OCT inhibitors.

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“…This has led the high demand for novel drugs with enhanced, targeted activity. Thiosemicarbazones (TSC) are very promising molecules having interesting pharmacological properties with remarkable antioxidant, antiviral, antibacterial, anticancer, antitumor, antimalarial, ribonucleotide reductase enzyme inhibition, and antifungal activities when coordinated to metals but also in their absence 1‐7 . TSC are synthesized through condensation of thiosemicarbazides with aldehydes or ketones 1‐3 .…”

Section: Introductionmentioning

confidence: 99%

Sustained release of a thiosemicarbazone from antibacterial electrospun poly(lactic‐co‐glycolic acid) fiber mats

Barani

Haseloer

Mathur

et al. 2020

Polymers for Advanced Techs

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Antibacterial fiber mats of poly(lactic-co-glycolic acid) (PLGA) were produced in the presence of different amounts of the thiosemicarbazone (TSC) N4-(S)-(1-phenylethyl)-2-(pyridin-2-ylmethylene)hydrazine-1-carbothioamide (HfpyTSCmB) through electrospinning. Increasing amounts (0, 2.5, 5, and 10 wt%) of TSC in the PLGA spinning solution in 2,2,2-trifluoroethanol (TFE) caused an increase up to 230% in conductivity and up to 27% in viscosity. The morphology of the electrospun fibers was studied using scanning electron microscope (SEM) and showed the formation of uniform, bead free, cylindrical, and smooth fiber mats. Increasing amounts of HfpyTSCmB in the polymer solution resulted also in significant shrinking of the diameter and narrowing of the size distribution of the fibers in line with the increased conductivity of the spinning solutions. Nuclear magnetic resonance (NMR) spectroscopy and thermal methods (DSC and TG/DTA) gave proof for the chemical integrity of HfpyTSCmB in the fiber mats after the electrospinning process. The release profile of HfpyTSCmB from the fibers was examined using UV-vis absorption spectroscopy. The observed release data during 21 days was fitted to different mathematical models with the best results obtained from the Higuchi release model. The fiber mat samples showed effective antibacterial properties with inhibition zones of 0.5 to 1.5 mm against the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli. K E Y W O R D S bacteriostatic properties, controlled drug release, nano fiber mats, PLGA, thiosemicarbazone 1 | INTRODUCTION There is an increasing demand for novel antimicrobial materials in many application areas, due to threatening human health with the growth of drug-resistant pathogens due to the biological and morphological modifications. This has led the high demand for novel drugs with enhanced, targeted activity. Thiosemicarbazones (TSC) are very promising molecules having interesting pharmacological properties with remarkable antioxidant, antiviral, antibacterial, anticancer, antitumor, antimalarial, ribonucleotide reductase enzyme inhibition, and antifungal activities when coordinated to metals but also in their absence. 1-7 TSC are synthesized through condensation of thiosemicarbazides with aldehydes or ketones. 1-3 The source thiosemicarbazides are synthesized either from secondary amines in a substitution reaction with methyl hydrazinecarbodithioate or from the addition of hydrazine to isothiocyanates. 6-13 TSC can act as ligands coordinating metal ions through their azomethine nitrogen and thiocarbonyl sulfur atoms (Scheme 1). The title TSC N4-(S)-(1-phenylethyl)-2-(pyridin-2-ylmethylene)hydrazine-1-carbothioamide (HfpyTSCmB) potentially coordinates metals through three (NNS)

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Multi-target compounds acting in cancer progression: Focus on thiosemicarbazone, thiazole and thiazolidinone analogues

Cited by 109 publications

References 85 publications

Characterization and Release Behavior of a Thiosemicarbazone from Electrospun Polyvinyl Alcohol Core-Shell Nanofibers

Characterization and Release Behavior of a Thiosemicarbazone from Electrospun Polyvinyl Alcohol Core-Shell Nanofibers

Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters

Sustained release of a thiosemicarbazone from antibacterial electrospun poly(lactic‐co‐glycolic acid) fiber mats

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