1,2,4-Triazol halkası taşıyan bazı üre ve tiyoüre türevleri ve anti-asetilkolinesteraz aktiviteleri

1,2,4-Triazol halkası taşıyan bazı üre ve tiyoüre türevleri ve anti-asetilkolinesteraz aktiviteleri Amaç: Yirmi adet farklı tiyoüre ve üre türevleri sentezlenmiş ve asetilkolinesteraz enzimini (AChE) inhibe etme yetenekleri Ellman’ın modifiye spektrofotometrik yöntemi ile değerlendirilmiştir. Yöntem: Anti-asetilkolinesteraz aktivite tayini Ellman’ın modifiye edilmiş spektrofotometrik yöntemi kullanılarak yapılmıştır. Bu spektrofotometrik yöntem bir kromojenik reaktif olan 5,5- dithiobis-(2-nitrobenzoik asit) ile salınan tiyokolinin renkli bir ürün vermesi esasına dayanır. Bulgular: Sentezlenen bileşiklerin (1a-e, 2a-e, 3a-e ve 4a-4e) anti-asetilkolinesteraz aktivite tayini Ellman’ın modifiye edilmiş spektrofotometrik yöntemi kullanılarak yapılmıştır. Test edilen bileşikler arasında, (4-{[(4-triflorometilfenil)karbamoil]amino} fenil)asetik asit (1d), en yüksek aktivite gösteren bileşik olmuştur. Bileşik 1d’nin 0.1mM konsantrasyonda inhibisyon oranı %48.55 olarak hesaplanmıştır. Sonuç: Anti-asetilkolinesteraz aktivite tarama sonuçları incelediğinde, fenil halkasının 4. konumunda triflorometil grubu taşıyan bileşik 1d’nin kaydadeğer anti-asetilkolinesteraz aktivite gösterdiği tespit edilmiştir. Aktivite sonuçları incelendiğinde, fenil halkası üzerinde halojen taşıyan yapıların anti-asetilkolinesteraz aktiviteyi arttırıcı yönde katkı sağladığı gözlenmektedir

N′-[(5-Methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)(thio­phen-2-yl)methyl­idene]benzohydrazide

In the title compound, C22H18N4O2S, the seven-membered ring generated by an intra­molecular N—H⋯O hydrogen bond adopts an envelope conformation in both of the two independent mol­ecules in the asymmetric unit. In the crystal, mol­ecules are linked into C(9) chains along [100] by N—H⋯O hydrogen bonds. The mol­ecules are also weakly linked by C—H⋯O and C—H⋯N inter­actions, forming dimers with edge-connected R 2 2(9) rings. The dimers are inter­linked by further weak C—H⋯N hydrogen bonds into chains along [010]

Synthesis and Biological Activity of Substituted Urea and Thiourea Derivatives Containing 1,2,4-Triazole Moieties

A series of novel thiourea and urea derivatives containing 1,2,4-triazole moieties were synthesized and evaluated for their antifungal and larvicidal activity. Triazole derivatives 3a–e and 4a–e were synthesized by reacting thiocarbohydrazide with thiourea and urea compounds 1a–e and 2a–e, respectively, in a 130–140 °C oil bath. The proposed structures of all the synthesized compounds were confirmed using elemental analysis, UV, IR, 1H-NMR and mass spectroscopy. All compounds were evaluated for antifungal activity against plant pathogens, larvicidal and biting deterrent activity against the mosquito Aedes aegypti L. and in vitro cytotoxicity and anti-inflammatory activity against some human cell lines. Phomopis species were the most sensitive fungi to these compounds. Compounds 1b, 1c, 3a and 4e demonstrated selectively good activity against Phomopis obscurans and only 1b and 4e showed a similar level of activity against P. viticola. Compound 3d, with a LD50 value of 67.9 ppm, followed by 1c (LD50 = 118.8 ppm) and 3e (LD50 = 165.6 ppm), showed the highest toxicity against Aedes aegypti larvae. Four of these compounds showed biting deterrent activity greater than solvent control, with the highest activity being seen for 1c, with a proportion not biting (PNB) value of 0.75, followed by 1e, 2b and 1a. No cytotoxicity was observed against the tested human cancer cell lines. No anti-inflammatory activity was observed against NF-kB dependent transcription induced by phorbol myristate acetate (PMA) in human chondrosarcoma cells

Synthesis and anticonvulsant activity of some 2-pyrazolines derived from chalcones

Synthesis of chalcones (1,3-diarylprop-2-en-1-ones) and 2-pyrazoline derivatives has been an active field of research due to their established pharmacological effects. In this study, a series of chalcones were prepared with methyl aryl ketones and substituted aldehydes in the presence of sodium hydroxide and methanol through Claisen-Schmidt condensation. 3,5-Disubstituted-4,5-dihydro-1H-pyrazole-1-carbothioamides were synthesized by refluxing selected chalcones and thiosemicarbazide in alkaline medium. Similarly N-3,5-trisubstituted-4,5-dihydro-1H-pyrazole-1-carboxamides were synthesized by refluxing selected chalcones with N-(4-chlorophenyl)semicarbazide in alkaline medium. Structures of the synthesized compounds were confirmed by elemental analysis and spectral (UV, IR, 1H NMR, 13C NMR, and mass) data, which were in line with the proposed structures. All compounds were tested for their anticonvulsant activity using pentylenetetrazole induced seizure (PTZ) and maximal electroshock seizure (MES) tests in mice at a dose level of 50 mg/kg. Among the 2-pyrazoline-1-carbothioamide derivatives, 5-(2,6-dichlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (2e) reduced grade-5 seizure activity and also increased survival rate in PTZ test. In MES test, 5-(4-methoxyphenyl)-3-[4-(methylsulphonyl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide(2g) has not only decreased seizure severity, but also increased survival rate. Among the 2-pyrazoline-1-carboxamide derivatives, 3-(5-bromothiophen-2-yl)-N-(4-chlorophenyl)-5-(2,6-dichlorophenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide (3d) having 5-bromothiophen and 2,6-dichlorophenyl moieties and N-(4-chlorophenyl)-5-(2,6-dichlorophenyl)-3-(5-chlorothiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carboxamide (3e) having 5-chlorothiophen and 2,6-dichlorophenyl moieties showed remarkable activities in PTZ test. Among all tested derivatives, compound 3d was found to be the most active one and reduced grade-5 seizure severity and also increased survival rate