Design, synthesis, anticonvulsant evaluation and docking study of 2-[(6-substituted benzo[ d ]thiazol-2-ylcarbamoyl)methyl]-1-(4-substituted phenyl)isothioureas

Siddiqui, Nadeem; Alam, Shamsher; Sahu, Meeta; Naim, Mohd. Javed; Yar, Mohammad Shahar; Alam, Ozair

doi:10.1016/j.bioorg.2017.02.009

Cited by 27 publications

(9 citation statements)

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“…Thiourea derivatives are a class of privileged compounds, exhibiting a wide range of biological activities, such as antibacterial [ 9 ], antifungal [ 10 ], antituberculosis [ 11 ], antiviral [ 12 ], anticancer [ 13 ], anti-parasitic [ 14 ], anticonvulsant [ 15 ], anti-oxidant [ 16 ], analgesic [ 17 ] and anti-inflammatory [ 18 ]. Thiourea derivatives also display good coordination ability, being used as intermediates for a great variety of heterocyclic products, such as thiohydantoin [ 19 ], iminothiazolidinone [ 20 ], thioxopyrimidindione, 1,2,4-thiadiazoles [ 19 ], 2 H -1,2,4-thiadiazolo[2,3- a ]pyrimidine [ 21 ] etc.…”

Section: Introductionmentioning

confidence: 99%

Novel Hybrid Formulations Based on Thiourea Derivatives and Core@Shell Fe3O4@C18 Nanostructures for the Development of Antifungal Strategies

et al. 2018

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The continuously increasing global impact of fungal infections is requiring the rapid development of novel antifungal agents. Due to their multiple pharmacological activities, thiourea derivatives represent privileged candidates for shaping new drugs. We report here the preparation, physico-chemical characterization and bioevaluation of hybrid nanosystems based on new 2-((4-chlorophenoxy)methyl)-N-(substituted phenylcarbamo-thioyl)benzamides and Fe3O4@C18 core@shell nanoparticles. The new benzamides were prepared by an efficient method, then their structure was confirmed by spectral studies and elemental analysis and they were further loaded on Fe3O4@C18 nanostructures. Both the obtained benzamides and the resulting hybrid nanosystems were tested for their efficiency against planktonic and adherent fungal cells, as well as for their in vitro biocompatibility, using mesenchymal cells. The antibiofilm activity of the obtained benzamides was dependent on the position and nature of substituents, demonstrating that structure modulation could be a very useful approach to enhance their antimicrobial properties. The hybrid nanosystems have shown an increased efficiency in preventing the development of Candida albicans (C. albicans) biofilms and moreover, they exhibited a good biocompatibility, suggesting that Fe3O4@C18core@shell nanoparticles could represent promising nanocarriers for antifungal substances, paving the way to the development of novel effective strategies with prophylactic and therapeutic value for fighting biofilm associated C. albicans infections.

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Section: Introductionmentioning

confidence: 99%

Novel Hybrid Formulations Based on Thiourea Derivatives and Core@Shell Fe3O4@C18 Nanostructures for the Development of Antifungal Strategies

et al. 2018

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“…Benzothiazole derivatives have been extensively studied in drug chemistry 1 , 2 and they exhibit diverse activities such as antitubercular 3 , antimicrobial 4–6 , antimalarial 7 , anticonvulsant 8 , antioxidant 9 , antidiabetic 10 , antitumor 11 , carbonic anhydrase (CA) 12 , and tryptase inhibitors 13 . Moreover, benzothiazole moieties are also found in fluorescent pH indicators 14 , iminocoumarin based zinc sensors 15 , bioluminogenic agent 16 , 17 , vulcanisation process of rubber 18 and ligands for transition metal catalysts 19 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis carbonic anhydrase enzyme inhibition and antioxidant activity of novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine moieties

Payaz

Küçükbay

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Thirteen novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine were synthesised by facile acylation reactions through benzotriazole or DCC mediated reactions and their structures were identified by 1 H-NMR, 13C-NMR, and FT-IR spectroscopic techniques and elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA V, and hCA XIII. Some of the synthesised compounds showed good in vitro carbonic anhydrase inhibitory properties, with inhibition constants in the micromolar level. The new amino acid benzothiazole conjugates found to be more effective against hCA V and hCA II inhibition. In vitro antioxidant activities of the novel compounds were determined by DPPH method. Most of the synthesised compounds showed moderate to low antioxidant activities compared to the control antioxidant compounds (BHA and a-tocopherol).

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“…Epilepsy is a common and chronic brain disorder characterized by unpredictable recurrent seizures (Abd‐Allah, Aboutabl, Aboul‐Enein, & El‐Azzouny, ). Despite the presence of many antiepileptic drugs (AEDs), approximately 30% of patients still suffer from uncontrolled episodes (Abd‐Allah et al, ; Abram et al, ; Siddiqui et al, ; Waszkielewicz et al, ). Moreover, AEDs have numerous undesirable side effects including neurotoxicity, which is very common and dose‐dependent (Edayadulla & Ramesh, ; Sangh Partap, Akhtar, Yar, Hassan, & Siddiqui, ; Rybka et al, ; St Louis, ).…”

Section: Introductionmentioning

confidence: 99%

“…Many studies to identify pharmacophores responsible for antiepileptic activity have been carried out. The common structural features are the presence of a hydrogen bonding domain (usually an amide), an electron donor and one or two aryl rings (He et al, ; Malawska, ; Obniska et al, ; Rybka, Obniska, Rapacz, Filipek, & Żmudzki, ; Siddiqui et al, ; Figure a).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, in vivo and in silico evaluation of novel 2,3‐dihydroquinazolin‐4(1H)‐one derivatives as potential anticonvulsant agents

Kothayer

Ibrahim

Soltan

et al. 2018

Drug Development Research

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In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N‐(1‐methyl‐4‐oxo‐2‐un/substituted‐1,2‐dihydroquinazolin‐3[4H]‐yl)benzamide (4a‐g) and N‐(1‐methyl‐4‐oxo‐2‐un/substituted‐1,2‐dihydroquinazolin‐3[4H]‐yl)‐2‐phenylacetamide (4h‐n) derivatives were synthesized in two steps starting from the reaction of N‐methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED50) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b, 4a, 4c, 4f, 4j, and 4i, showed very low ED50 values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABAA binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier. Hit, Lead & Candidate Discovery

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Design, synthesis, anticonvulsant evaluation and docking study of 2-[(6-substituted benzo[ d ]thiazol-2-ylcarbamoyl)methyl]-1-(4-substituted phenyl)isothioureas

Cited by 27 publications

References 30 publications

Novel Hybrid Formulations Based on Thiourea Derivatives and Core@Shell Fe3O4@C18 Nanostructures for the Development of Antifungal Strategies

Novel Hybrid Formulations Based on Thiourea Derivatives and Core@Shell Fe3O4@C18 Nanostructures for the Development of Antifungal Strategies

Synthesis carbonic anhydrase enzyme inhibition and antioxidant activity of novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine moieties

Synthesis, in vivo and in silico evaluation of novel 2,3‐dihydroquinazolin‐4(1H)‐one derivatives as potential anticonvulsant agents

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