- Synthesis and Antiproliferative Activity of New Thiosemicarboxamide Derivatives
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To discover new anticancer agents, two series of thiosemicarboxamide derivatives were synthesized and evaluated for their antiproliferative activity against human cancer cells in vitro. Most target compounds (especially 3f, 3g, and 3h) exhibit potent antiproliferative activity against HeLa cells. Importantly, compound 3h, bearing a 4-methylphenyl substituent at N position of thiourea moiety, has significant and broad-spectrum inhibitory activities against cancer cells (HepG2, HeLa, MDA-MB231, A875, and H460 cells) with low IC50 values (5.0 μM) and shows low toxicity to normal LO2 and MRC-5 cells. Further studies show that compound 3h exerts high inhibitory activity in cancer cells by inducing the G2/M-phase arrest of cancer cells. Collectively, this study presents compound 3h as a new entity for the development of cell cycle arrest inducers for the treatment of cancer.
- Chen, Jun,Fang, Meijuan,Guo, Yafei,Hu, Hongyu,Hu, Sangsang,Sun, Ke,Wu, Jun,Xue, Yuhua
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- Synthesis, characterization, and antioxidant activity of some new N 4-arylsubstituted-5-methoxyisatin-β-thiosemicarbazone derivatives
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Abstract: Firstly, thiosemicarbazides were prepared by the reaction of hydrazine monohydrate with isothiocyanates in cold dry ethanol at 0?°C for 1?h. After that, new isatin-β-thiosemicarbazones were synthesized by treatment of 5-methoxyisatin with thiose
- Mu?lu, Halit
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p. 2083 - 2098
(2020/01/13)
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- Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents
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In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial–mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer.
- Bo-Wang,He, Zhang-Xu,Li, Yi-Han,Liu, Hong-Min,Ma, Li-Ying,Ma, Qin,Tao, Yuan-Yuan,Wang, Hao-Jie,Wu, Hui-Pan,Zhang, Xin-Hui,Zhao, Bing
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- Preparation, structure elucidation, and antioxidant activity of new bis(thiosemicarbazone) derivatives
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Schiff-base–bearing new bis(thiosemicarbazone) derivatives were prepared from terephthalaldehyde and various thiosemicarbazides. FT–IR, 1 H NMR, 13 C NMR, and UV–Vis spectroscopic methods and elemental analysis were used to elucidate
- Yakan, Hasan
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p. 1085 - 1099
(2020/09/16)
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- INDOLE-OXADIAZOLE COMPOUNDS AND THEIR THERAPEUTIC USE
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The present application pertains to methods of using indole-oxadiazole compounds of Formula I to modulate cannabinoid receptor activity: I In particular diseases, disorders or conditions that benefit from modulating cannabinoid receptor activity, such as non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), schizophrenia, bipolar disorder, psychosis, metabolic syndrome, type-2 diabetes, dyslipidaemia, obesity, eating disorders, cardiovascular diseases and disorders, and other conditions as described herein, may be treated. Also included in the present application are certain novel compounds of Formula Ia and pharmaceutical compositions comprising these compounds.
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Paragraph 00184; 00189; 00199
(2020/05/07)
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- Preparation and antitubercular activities of palindromic hydrazinecarbothioamides and carbonothioic dihydrazides
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Background: With approximately one-third of the world’s population infected, tuberculosis continues to be a global public health crisis. The rise of strains that are unusually virulent or highly resistant to current drugs is a cause of special concern, pr
- Hearn, Michael Joseps,Towers, Gwendolyn,Cynamon, Michael Henry
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p. 1202 - 1210
(2019/11/22)
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- Novel thiosemicarbazone derivatives containing indole fragment as potent and selective anticancer agent
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Potent and safe anticancer drugs research and development are still on the way to human health. In this report, a series of novel thiosemicarbazone derivatives containing indole fragment were designed and synthesized. Most compounds exhibited excellent antiproliferative activity against PC3, MGC803 and EC109 cell lines with low micromolar IC50 (0.14–12μM). Especially, compound 5j can selectively inhibit PC3 cells in three tested tumor cells with IC50 value of 0.14 μM, which may be attributed to a synergistic effect after introducing indole fragment into the TSC structure. Meanwhile, compound 5j displayed more selectivity in PC3 cells toward two normal WPMY-1 and GES-1 cell lines, compared to those of 3-AP and DPC. We also found that 5j can effectively inhibit PC3 cell proliferation, colonization and induce apoptosis. What's more, 5j may significantly suppress migration and invasion by blocking the EMT process but had no effect on cell cycle. Collectively, our findings indicate that 5j with structure of thiosemicarbazone containing indole may serve as a useful anticancer lead for further optimization and development.
- He, Zhangxu,Qiao, Hui,Yang, Feifei,Zhou, Wenjuan,Gong, Yunpeng,Zhang, Xinhui,Wang, Haojie,Zhao, Bing,Ma, Liying,Liu, Hong-min,Zhao, Wen
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- Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition
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Twelve 2-(quinolin-4-ylmethylene) hydrazinecarbothioamide derivatives were synthetized and their biological properties were investigated, among which, the ability to interact with DNA and BSA through UV–Vis absorption, fluorescence, Circular Dichroism, molecular docking and relative viscosity, antiproliferative activity against MCF-7 and T-47D mammary tumor cells and RAW-264.7 macrophages and inhibitory capacity of the enzyme topoisomerase IIα. In the binding study with DNA and BSA, all the compounds displayed affinity for interaction with both biomolecules, especially JF-92 (p-ethyl-substituted), with binding constant of 1.62 × 106 and 1.43 × 105, respectively, and DNA binding mode by intercalation. The IC50 values were obtained between 0.81 and 1.48 μM and topoisomerase inhibition results in 10 μM. Thus, we conclude that the reduction of the acridine to quinoline ring did not disrupt the antitumor action and that substitution patterns are important for biomolecule interaction affinity as they demonstrate the potential of these compounds for anticancer therapy.
- Ribeiro, Amélia Galdino,Almeida, Sinara M?nica Vitalino de,de Oliveira, Jamerson Ferreira,Souza, Tulio Ricardo Couto de Lima,Santos, Keriolaine Lima dos,Albuquerque, Amanda Pinheiro de Barros,Nogueira, Mariane Cajuba de Britto Lira,Carvalho Junior, Luiz Bezerra de,Moura, Ricardo Olímpio de,da Silva, Aline Caroline,Pereira, Valéria Rêgo Alves,Castro, Maria Carolina Accioly Brelaz de,Lima, Maria do Carmo Alves de
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- Inhibitory properties of aromatic thiosemicarbazones on mushroom tyrosinase: Synthesis, kinetic studies, molecular docking and effectiveness in melanogenesis inhibition
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The group of 19 thiosemicarbazones (TSCs) were synthesized and its inhibitory activity toward mushroom tyrosinase and ability to inhibition of melanogenesis in B16 cells were investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. The obtained results allowed to make the structure-activity relationship (SAR) analysis. Kinetic studies revealed that TSCs 1, 2, 11 and 18 have better inhibitory properties than kojic acid, a reference compound, with the best inhibitory constant (Ki) value of 0.38 μM for TSC 2. According to SAR analysis, the smaller and less branched molecules exhibit higher affinity to the enzyme. Melanin production in B16 cells was inhibited by all investigated compounds at micromolar level. Most of compounds studied in this work can be considered as potent inhibitors of tyrosinase and melanogenesis. They may have broad application in food preservatives and cosmetics. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties.
- Ha?dys,Goldeman,Jewgiński,Wolińska,Anger,Rossowska,Latajka
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p. 577 - 586
(2018/09/29)
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- Thiosemicarbazones and 4-thiazolidinones indole-based derivatives: Synthesis, evaluation of antiproliferative activity, cell death mechanisms and topoisomerase inhibition assay
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In this study, we report the synthesis and structural characterization of a series of thiosemicarbazone and 4-thiazolidinones derivatives, as well as their in?vitro antiproliferative activity against eight human tumor cell lines. For the most potent compo
- de Oliveira, Jamerson Ferreira,Lima, Talitha Santos,Vendramini-Costa, Débora Barbosa,de Lacerda Pedrosa, Sybelle Christianne Batista,Lafayette, Elizabeth Almeida,da Silva, Rosali Maria Ferreira,de Almeida, Sinara Monica Vitalino,de Moura, Ricardo Olímpio,Ruiz, Ana Lúcia Tasca Gois,de Carvalho, Jo?o Ernesto,de Lima, Maria do Carmo Alves
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p. 305 - 314
(2017/05/16)
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- Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities
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A series of thiophene-2-thiosemicarbazones derivatives (5-14) was synthesized, characterized and evaluated for their antitumor activity. They were tested in vitro against human tumor cell lines through the colorimetric method. The results revealed that compounds 7 and 9 were the most effective in inhibiting 50% of the cell growth after 48 h of treatment. As compound 7 showed a potent antiproliferative profile, it has been chosen for further studies in 786-0 cell line by flow cytometry. Treatments with compound 7 (50 μM) induced early phosphatidylserine exposure after 18 h of exposure and this process progressed phosphatidylserine exposure with loss of cell membrane integrity after 24 h of treatment, suggesting a time-dependent cell death process. Regarding the cell cycle profile, no changes were observed after treatment with compound 7 (25 μM), suggesting a mechanism of cell death independent on the cell cycle. The in vivo studies show that compound 7 possess low acute toxicity, being the doses of 30-300 mgKg-1 chosen for studies in Ehrlich solid tumor model in mice. All doses were able to inhibit tumor development being the lowest one the most effective. Our findings highlight thiophene-2-thiosemicarbazones as a promising class of compounds for further studies concerning new anticancer therapies.
- De Oliveira, Jamerson Ferreira,Da Silva, Anekécia Lauro,Vendramini-Costa, Débora Barbosa,Da Cruz Amorim, Cezar Augusto,Campos, Júlia Furtado,Ribeiro, Amélia Galdino,De Moura, Ricardo Olímpio,Neves, Jorge Luiz,Ruiz, Ana Lúcia Tasca Gois,De Carvalho, Jo?o Ernesto,Alves De Lima, Maria Do Carmo
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p. 148 - 156
(2015/10/29)
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- Thiosemicarbazones as effective fluorescent sensors for cations and anions
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Abstract- Series of anthracene-containing chemosensors was synthesized by the reaction of 4-Rthiosemicarbazides with aromatic aldehydes. Spectral studies showed their high sensory activity with respect to a group of cations and anions like Hg2+, F-, CN-, AcO- etc. Pleiades Publishing, Ltd., 2012.
- Tolpygin
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p. 1533 - 1536
(2013/01/15)
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- Synthesis, spectral, thermal and anti-fungal studies of organotin(IV) thiohydrazone complexes
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The reaction of tribenzyltin(IV) chloride and di(para-chlorobenzyl)tin(IV) dichloride with thiohydrazones derived by condensation of 2-phenylethyl N-thiohydrazide with benzaldehyde, salicaldehyde, p-methylacetophenone and cinnamaldehyde have been investig
- Singh, Rajeev,Kaushik
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experimental part
p. 691 - 696
(2009/05/06)
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- Spectral and thermal studies with anti-fungal aspects of some organotin(IV) complexes with nitrogen and sulphur donor ligands derived from 2-phenylethylamine
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Some complexes of 2-phenylethyl dithiocarbamate, thiohydrazides and thiodiamines with dibenzyltin(IV) chloride, tribenzyltin(IV) chloride and di(para-chlorobenzyl)tin(IV) dichloride have been synthesized and investigated in 1:2 and 1:1 molar ratio. The di
- Singh, Rajeev,Kaushik
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experimental part
p. 669 - 675
(2009/02/07)
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- Organotin(IV) complexes of thiohydrazides and thiodiamines: synthesis, spectral and thermal studies
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Organotin(IV) complexes of tribenzyltin(IV) chloride and di(para-chlorobenzyl)tin(IV) dichloride with thiohydrazides have been reported. The ligands synthesized were bidentate coordinating through sulphur and terminal nitrogen atoms. These form 1:1 metal-
- Singh, Rajeev,Kaushik
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p. 950 - 954
(2007/10/03)
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- Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors
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The synthesis and enzyme inhibition data for a series of thiadiazole urea matrix metalloproteinase (MMP) inhibitors are described. A broad screening effort was utilized to identify several thiadiazoles which were weak inhibitors of stromelysin. Optimization of the thiadiazole leads to include an α-amino acid side chain with variable terminal amide substituents provided a series of ureas which were moderately effective stromelysin inhibitors, with K(i)'s between 0.3 and 1.0 μM. The most effective analogues utilized an L-phenylalanine as the amino acid component. In particular, unsubstituted 46 had a K(i) of 710 nM, while the p-fluoro analogue 52 displayed increased potency (100 nM). Stromelysin inhibition was further improved using a pentafluorophenylalanine substituent which resulted in 70, a 14 nM inhibitor. While gelatinase inhibition was generally poor, the use of 1-(2-pyridyl)piperazine as the amide component usually provided for enhanced activity, with 71 inhibiting gelatinase with a K(i) of 770 nM. The combination of this heterocycle with a p-fluorophenylalanine substituent provided the only analogue, 69, with collagenase activity (13 μM). The SAR for analogues described within this series can be rationalized through consideration of the X-ray structure recently attained for 70 complexed to stromelysin. Uniquely, this structure showed the inhibitor to be completely orientated on the left side of the enzyme cleft. These results suggest that thiadiazole urea heterocycles which incorporate a substituted phenylalanine can provide selective inhibitors of stromelysin. Careful selection of the amide substituent can also provide for analogues with modest gelatinase inhibition.
- Jacobsen, E. Jon,Mitchell, Mark A.,Hendges, Susan K.,Belonga, Kenneth L.,Skaletzky, Louis L.,Stelzer, Lindsay S.,Lindberg, Thomas J.,Fritzen, Edward L.,Schostarez, Heinrich J.,O'Sullivan, Theresa J.,Maggiora, Linda L.,Stuchly, Christopher W.,Laborde, Alice L.,Kubicek, Marc F.,Poorman, Roger A.,Beck, Joan M.,Miller, Henry R.,Petzold, Gary L.,Scott, Pam S.,Truesdell, Scott E.,Wallace, Tanya L.,Wilks, John W.,Fisher, Christopher,Goodman, Linda V.,Kaytes, Paul S.,Ledbetter, Stephen R.,Powers, Elaine A.,Vogeli, Gabriel,Mott, John E.,Trepod, Catherine M.,Staples, Douglas J.,Baldwin, Eric T.,Finzel, Barry C.
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p. 1525 - 1536
(2007/10/03)
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- Synthesis of 4-Substituted Thiosemicarbazones of 3-Methyl-4-phenylpyridine-2-carboxaldehyde as Antitumor Agents
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A convenient synthesis of 3-methyl-4-phenylpyridine-2-carboxaldehyde (4) is described.Reaction of 4 with 4-substituted thiosemicarbazides (6) gives thiosemicarbazones (7) some of which (7b, 7g, 7i and 7j) exhibit significant antitumor activity in animals.Thiosemicarbazides (6e - 6j) have been prepared from the corresponding isothiocyanates (5) (which result from sodium chlorite oxidation of the addition products of CS2 and the appropriate amine) and hydrazine.Isomerisation of 1,3-dimethyl-4-phenyl-1,2,3,6-tetrahydropyridine (Δ4-isomer) to 1,2,5,6-tetrahydro analog (Δ3-isomer, 1) has been effected with refluxing conc.HCl.
- Rahman, M. F.
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p. 828 - 830
(2007/10/02)
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