38985-70-5Relevant academic research and scientific papers
Synthesis and evaluation of new 1,3,4-thiadiazole derivatives as antinociceptive agents
Altintop, Mehlika Dilek,Can, ?zgür Devrim,?zkay, ümide Demir,Kaplancikl, Zafer Asim
, (2016)
In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were eval
Synthesis, characterization, and antioxidant activity of some new N 4-arylsubstituted-5-methoxyisatin-β-thiosemicarbazone derivatives
Mu?lu, Halit
, p. 2083 - 2098 (2020/01/13)
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
Synthesis of novel quinoline-thiosemicarbazide hybrids and evaluation of their biological activities, molecular docking, molecular dynamics, pharmacophore model studies, and ADME-Tox properties
Darji, Drashti G.,Patel, Dhaval B.,Patel, Hitesh D.,Patel, Krupa R.,Rajani, Dhanji P.,Rajani, Smita D.
, (2020/02/13)
In the present study, a novel series of N-((substituted)carbamothioyl)-2,4-dimethylquinoline-3-carboxamide (7a-7s) was synthesized by microwave-assisted method. Structure of these derivatives was examined by spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and ESI-MS. Further, the novel synthesized compounds were evaluated for their in-vitro biological activities against antibacterial, antifungal, antimalarial, and antituberculosis activity as well as for in-silico study. The antimalarial results demonstrated that compounds 7c and 7q (0.02 μg/mL) have notable potency against Plasmodium falciparum compared with chloroquine (0.02 μg/mL); compounds 7l (0.10 μg/mL), 7e, 7s (0.19 μg/mL), 7b, 7p (0.15 μg/mL), 7a, 7f, and 7f (0.25 μg/mL) also exhibited good activity against P. falciparum compared with quinine (0.26 μg/mL) as standard drug. Docking was performed on PFDHFR-TS, given the effect of compounds against the P. falciparum strain was excellent in comparison with standard drug. Molecular docking suggested that compounds 7b, 7i and 7c, 7e, and 7l closely bind with the active site of protein 3JSU and 4DP3, respectively, and compared with biological activity. We have also carried out molecular dynamics simulation on the best dock compound 7e complex with PDB: 3JSU to check the stability of docked complex and their molecular interaction. The calculated ADME-Tox descriptors for the synthesized compounds validated good pharmacokinetics properties, suggesting that these compounds could be used as hit for the development of the new active agents.
Preparation, structure elucidation, and antioxidant activity of new bis(thiosemicarbazone) derivatives
Yakan, Hasan
, p. 1085 - 1099 (2020/09/16)
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
Functionalized Oxoindolin Hydrazine Carbothioamide Derivatives as Highly Potent Inhibitors of Nucleoside Triphosphate Diphosphohydrolases
Afzal, Saira,Hameed, Abdul,Iqbal, Jamshed,Pelletier, Julie,Sévigny, Jean,al-Rashida, Mariya
, (2020/12/18)
Ectonucleoside triphosphate diphosphohydrolases (NTPDases) are ectoenzymes that play an important role in the hydrolysis of nucleoside triphosphate and diphosphate to nucleoside monophosphate. NTPDase1, -2, -3 and -8 are the membrane bound members of this enzyme family that are responsible for regulating the levels of nucleotides in extracellular environment. However, the pathophysiological functions of these enzymes are not fully understood due to lack of potent and selective NTPDase inhibitors. Herein, a series of oxoindolin hydrazine carbothioamide derivatives is synthesized and screened for NTPDase inhibitory activity. Four compounds were identified as selective inhibitors of h-NTPDase1 having IC50 values in lower micromolar range, these include compounds 8b (IC50 = 0.29 ± 0.02 μM), 8e (IC50 = 0.15 ± 0.009 μM), 8f (IC50 = 0.24 ± 0.01 μM) and 8l (IC50 = 0.30 ± 0.03 μM). Similarly, compound 8k (IC50 = 0.16 ± 0.01 μM) was found to be a selective h-NTPDase2 inhibitor. In case of h-NTPDase3, most potent inhibitors were compounds 8c (IC50 = 0.19 ± 0.02 μM) and 8m (IC50 = 0.38 ± 0.03 μM). Since NTPDase3 has been reported to be associated with the regulation of insulin secretion, we evaluated our synthesized NTPDase3 inhibitors for their ability to stimulate insulin secretion in isolated mice islets. Promising results were obtained showing that compound 8m potently stimulated insulin secretion without affecting the NTPDase3 gene expression. Molecular docking studies of the most potent compounds were also carried out to rationalize binding site interactions. Hence, these compounds are useful tools to study the role of NTPDase3 in insulin secretion.
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.
Synthesis of novel triazinoindole-based thiourea hybrid: A study on α-glucosidase inhibitors and their molecular docking
Taha, Muhammad,Alshamrani, Foziah J.,Rahim, Fazal,Hayat, Shawkat,Ullah, Hayat,Zaman, Khalid,Imran, Syahrul,Khan, Khalid Mohammed,Naz, Farzana
, (2019/11/11)
A new class of triazinoindole-bearing thiosemicarbazides (1-25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 μM when compared to standard acarbose (an IC50 value of 38.60 ± 0.20 μM). Among the series, analogs 1 and 23 were found to be the most potent, with IC50 values of 1.30 ± 0.05 and 1.30 ± 0.01 μM, respectively. The structure- activity relationship (SAR) was mainly based upon bringing about different substituents on the phenyl rings. To confirm the binding interactions, a molecular docking study was performed.
3-[(E)-(acridin-9′-ylmethylidene)amino]-1-substituted thioureas and their biological activity
Be?ka, Michal,Vilková, Mária,Salem, Othman,Ka?párková, Jana,Brabec, Viktor,Ko?urková, Mária
, p. 234 - 241 (2017/03/23)
This paper describes the synthesis of a novel series of acridine thiosemicarbazones through a two-step reaction between various isothiocyanates and hydrazine followed by treatment with acridin-9-carbaldehyde. The properties of this series of seven new derivatives are studied using NMR and biochemical techniques, and the DNA-binding properties of the compounds are determined using spectrophotometric studies (UV–vis absorption, fluorescence, and circular/linear dichroism) and viscometry. The binding constants K are estimated as being in the range of 2.2 to 7.8?×?104?M??1 and the percentage of hypochromism was found to be 22.11–49.75% (from UV–vis spectral titration). Electrophoretic experiments prove that the novel compounds demonstrate moderate inhibitory effects against Topo I activity at a concentration of 60?×?10??6?M.
Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance
Pape, Veronika F.S.,Tóth, Szilárd,Füredi, András,Szebényi, Kornélia,Lovrics, Anna,Szabó, Pál,Wiese, Michael,Szakács, Gergely
, p. 335 - 354 (2016/05/19)
There is a constant need for new therapies against multidrug resistant (MDR) cancer. An attractive strategy is to develop chelators that display significant antitumor activity in multidrug resistant cancer cell lines overexpressing the drug efflux pump P-glycoprotein. In this study we used a panel of sensitive and MDR cancer cell lines to evaluate the toxicity of picolinylidene and salicylidene thiosemicarbazone, arylhydrazone, as well as picolinylidene and salicylidene hydrazino-benzothiazole derivatives. Our results confirm the collateral sensitivity of MDR cells to isatin-β-thiosemicarbazones, and identify several chelator scaffolds with a potential to overcome multidrug resistance. Analysis of structure-activity-relationships within the investigated compound library indicates that NNS and NNN donor chelators show superior toxicity as compared to ONS derivatives regardless of the resistance status of the cells.
Synthesis of Cyclic Azomethine Imines by Cycloaddition Reactions of N-Isocyanates and N-Isothiocyanates
Bongers, Amanda,Ranasinghe, Indee,Lemire, Philippe,Perozzo, Alyssa,Vincent-Rocan, Jean-Fran?ois,Beauchemin, André M.
supporting information, p. 3778 - 3781 (2016/08/16)
Various nitrogen-substituted iso(thio)cyanates engage in [3 + 2]-cycloaddition reactions to form azomethine imines containing triazolone, triazole-thione, and pyrazole-thione cores. First, iminoisothiocyanates are shown to undergo aminothiocarbonylation reactions with strained alkenes, and a comparison with recently reported reactions of iminoisocyanates highlights their reduced reactivity. In contrast, amino(thio)carbonylation reactions of imines with iminoisocyanates and iminoisothiocyanates proved more efficient, providing access to triazolone and triazole-thione cores. The dipole products can be converted to valuable heterocyclic cores through simple derivatization reactions.
