3766-55-0Relevant academic research and scientific papers
Insight on a new indolinone derivative as an orally bioavailable lead compound against renal cell carcinoma
Fouad, Marwa A.,Lotfy, Raghda A.,Mahmoud, Walaa R.,Zaki, Mayssoune Y.
, (2021/06/15)
A series of novel 3-indolinone-thiazolidinones and oxazolidinones 4a-k was synthesized via molecular hybridization approach and sequentially evaluated to explore its cytotoxic activity. The cytotoxicity screening pointed toward the N-cyclohexyl thiazolidinone derivative 4f that revealed promising renal cytotoxicity against CAKI-1 and UO-31 renal cancer cell lines with IC50 values 4.74 and 3.99 μM, respectively, which were comparable to those of sunitinib along with good safety threshold against normal renal cells. Further emphasis on compound 4f renal cytotoxicity was achieved via different enzyme assays and CAKI-1 and UO-31 cell cycle analysis. The results were supported by in silico studies to explore its physicochemical, pharmacokinetic and drug-likeness properties. Finally, compound 4f was subjected to an in vivo pharmacokinetic study through two different routes of administration showing excellent oral bioavailability. This research represents compound 4f as a promising candidate against renal cell carcinoma.
Anti-inflammatory activity of novel thiosemicarbazone compounds indole-based as COX inhibitors
Jacob, íris T. T.,Gomes, Fabiana O. S.,de Miranda, Mirelly D. S.,de Almeida, Sinara M. V.,da Cruz-Filho, Iranildo J.,Peixoto, Christina A.,da Silva, Teresinha G.,Moreira, Diogo R. M.,de Melo, Cristiane M. L.,de Oliveira, Jamerson F.,de Lima, Maria C. A.
, p. 907 - 925 (2021/02/26)
Background: In this article, a series of 20 new thiosemicarbazone derivatives containing indole were synthesized and evaluated for their anti-inflammatory potential. Methods: The compounds were obtained through a synthetic route of only two steps, with yields that varied between 33.6 and 90.4%, and characterized by spectroscopic and spectrometric techniques. Results: An initial screening through the lymphoproliferation assay revealed that compounds LT76, LT81, and LT87 were able to inhibit lymphocyte proliferation, with CC50 of 0.56 ± 0.036, 0.9 ± 0.01 and 0.5 ± 0.07?μM, respectively, better results than indomethacin (CC50 > 12?μM). In addition, these compounds were able to suppress the in-vitro production of TNF-α and NO, in addition to stimulating the production of IL-4. Reinforcing in-vitro assays, the compounds were able to inhibit COX-2 similar to Celecoxib showing greater selectivity for this isoform (LT81 SI: 23.06 versus Celecoxib SI: 11.88). Animal studies showed that compounds LT76 (64.8% inhibition after 6?h), LT81 (89% inhibition after 6?h) and LT87 (100% inhibition after 4?h) were able to suppress edema in mice after inoculation carrageenan with greater potency than indomethacin, and immunohistochemistry revealed that the groups treated with LT76, LT81 and LT87 reduced the expression of COX-2, similar or better results when compared to indomethacin. Complementarily, in-silico studies have shown that these compounds have a good pharmacokinetic profile, for respecting the parameters of Lipinski and Veber, showing their good bioavailability. Conclusions: These results demonstrate the potency of thiosemicarbazone derivatives containing indole and confirm their importance as scaffolds of molecules with notorious anti-inflammatory activity.
Synthesis and characterization of a new series of thiadiazole derivatives as potential anticancer agents
?evik, Ulviye Acar,Osmaniye, Derya,Levent, Serkan,Sa?lik, Begüm Nurpelin,?avu?o?lu, Betül Kaya,?zkay, Yusuf,Kaplancikl, Zafer Aslm
, p. 6 - 13 (2020/03/30)
Cancer is one of the most common causes of death in the world. Despite the importance of combating cancer in healthcare systems and research centers, toxicity in normal tissues and the low efficiency of anticancer drugs are major problems in chemotherapy. Nowadays the aim of many medical research projects is to discover new safer and more effective anticancer agents. 1,3,4-Thiadiazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities, including anticancer activities. The aim of this study was to determine the capacity of newly synthesized 1,3,4-thiadiazole compounds as chemotherapeutic agents. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and mass spectrometry. Although the thiadiazole derivatives did not prove to be significantly cytotoxic to the tumour tissue cultures, compound 4i showed activity against the C6 rat brain cancer cell line (IC50 0.097 mM) at the tested concentrations.
One-pot green synthesis of some novel n-substituted 5-amino-1,3,4-thiadiazole derivatives
Abdul Rahman, Mohd B.,Habibi, Azizollah,Khosravi, Sahar,Shahcheragh, Seyyed M.
supporting information, p. 517 - 522 (2020/07/17)
In the current study, a green, one-pot, three-component reaction was performed to prepare novel N-substituted 5-amino-1,3,4-thiadiazole derivatives. The thiadiazoles were obtained from the reaction of a ketene S,S-acetal of Meldrum’s acid or barbituric acid (as key intermediates), hydrazine, and isothiocyanate. The key advantages of this manner include environmentally safe reactions, high yield, appropriate reaction time, simple reaction conditions, and use of a green reaction solvent. The structure of thiadiazoles was determined based on the spectroscopic data.
Novel 1,3,4-thiadiazole compounds as potential MAO-A inhibitors-design, synthesis, biological evaluation and molecular modelling
Kaplancikli, Zafer Asim,Levent, Serkan,Osmaniye, Derya,?zkay, Yusuf,Acar ?evik, Ulviye,Kaya ?avu?o?lu, Betül,Sa?lik, Begüm Nurpelin
, p. 1063 - 1074 (2020/10/06)
Monoamine oxidases (MAOs) are important drug targets for the management of neurological disorders. Herein, a series of new 1,3,4-thiadiazole derivatives bearing various alkyl/arylamine moieties as MAO inhibitors were designed and synthesized. All of the compounds were more selective against hMAO-A than hMAO-B. The half maximal inhibitory concentration (IC50) values of most of the compounds were lower than that of the common drug moclobemide (IC50 = 4.664 μM) and compound 6b was proven to be the most active compound (IC50 = 0.060 μM). Moreover, it was seen that compound 6b showed a similar inhibition profile to that of clorgyline (IC50 = 0.048 μM). The inhibition profile was found to be reversible and competitive for compound 6b with MAO-A selectivity. Molecular modelling studies aided in the understanding of the interaction modes between compound 6b and MAO-A. Furthermore, this compound was predicted to have a good pharmacokinetic profile and high BBB penetration. Therefore, such compounds are of interest towards developing new MAO inhibitors.
Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition
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
, (2019/08/20)
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.
Solvated copper(I) hexafluorosilicate π-complexes based on [Cu2(amtd)2]2+ (amtd = 2-allylamino-5-methyl-1,3,4-thiadiazole) dimer
Goreshnik,Veryasov,Morozov,Slyvka,Ardan,Mys'kiv
, p. 1 - 11 (2016/03/22)
[Cu2(amdt)2]SiF6·C6H6 and [Cu2(amdt)2(H2O)2]SiF6·CH3CN·2H2O (amdt = 2-allylamino-5-methyl-1,3,4-thiadiazole) were obtained by alternating-current electrochemical synthesis, starting from water-acetonitrile-benzene mixtures containing 2-allylamino-5-methyl-1,3,4-thiadiazole and CuSiF6·4H2O. The electrochemical reduction of the saturated copper hexafluorosilicate water solution beneath the neatly poured layer of acetonitrile-benzene amdt solution resulted in the formation of crystalline [Cu2(amdt)2]SiF6·C6H6. The initial stirring of the same mixture before subjecting it to the electrochemical reduction resulted in the formation of [Cu2(amdt)2(H2O)2]SiF6·CH3CN·2H2O. A sluggish hydrolysis of the acetonitrile over 2 years in a closed test tube with [Cu2(amdt)2]SiF6·C6H6 crystals in a mother liquor resulted in the formation of [Cu2L2(H2O)2]SiF6·CH3CONH2·2H2O. All the compounds were studied using X-ray single-crystal diffraction and Raman spectroscopy. The molecular structures and the Raman spectra of the compounds were discussed on the basis of computational modeling with the DFT/B3LYP/cc-pVDZ method.
Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities
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
, p. 148 - 156 (2015/10/29)
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.
First nγ-allyl-aminothiadiazole copper(I) φ-complexes: Synthesis and structural peculiarities of [Cu(L)CF3SO3] and [Cu 2(L)2(H2O)2](SiF6) · 2.5H2O compounds (L = 2-(allyl)-amino-5-methyl-1,3,4-thiadiazole)
Ardan, Bogdan,Slyvka, Yuriy,Goreshnik, Evgeny,Mys'kiv, Marian
, p. 484 - 490 (2013/09/23)
By means of alternating current electrochemical technique two crystalline copper(I) φ-complexes with fluorine containing anions [Cu(L)CF 3SO3] (1) and [Cu2(L)2(H 2O)2](SiF6)2 · 2.5H 2O (2) (L - 2-(allyl)-amino-5-methyl-1,3,4-thiadiazole) have been obtained and characterized by X-ray single crystal diffraction and Raman spectroscopy. In both structures the organic molecule L acts as chelate-bridging tridentate ligand being connected to copper(I) by two N atoms of thiadiazole ring and C=C bond from allyl group resulting in a formation of stable cationic dimmers SsCu(L)c2]2+. In the structure 1 oxygen atom from triflate-anion occupies an apical position of the metal coordination polyhedron, while in 2 located far from the metal centre hexafluorosilicate anion allows an appearance of the H2O molecule in copper environment. Hydrogen bonds (D)-H···A (where D = O, N, C; A = O, F) play a significant role in formation of 2D- (1) and 3D- (2) frameworks.
Synthesis of novel spiro(indolone-3,2′-[1,3,4]thiadiazol)-2-ones and evaluation of their antidepressant and anticonvulsant activities
Hassan, Alaa A.,Abdel-Latif, Fathy F.,El-Din, Ahmed M. Nour,Abdel-Aziz, Mohamed,Mostafa, Sara M.,Braese, Stefan
experimental part, p. 1050 - 1055 (2011/11/06)
The reaction of 3-(dicyanomethylene)-2-indolone in a solution of ethanol/piperidine with 4-substituted thiosemicarbazides forms the derivatives of 5′-(substituted amino)-3′H-spiro(indoline-3,2′-[1,3,4] thiadiazol-2-one. Rationales for these conversions involving the nucleophilic addition on the dicyanomethylene carbon atom are presented. The prepared compounds were evaluated each for antidepressant activity using tail suspension behavioral despair test and anticonvulsant activity against pentylenetetrazol induced seizures in mice.
