Some urea and thiourea derivatives bearing 1,2,4-triazole ring and their anti-acetylcholinesterase activities

Abstract

ÖZET 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. Anahtar sözcükler: Üre, tiyoüre, 1,2,4-triazol, anti-asetilkolinesteraz aktivite ABS TRACT Some urea and thiourea derivatives bearing 1,2,4-triazole ring and their antiacetylcholinesterase activities Objective: Twenty different urea and thiourea derivatives were synthesized and evaluated for their ability to inhibit acetylcholinesterase (AChE) using a modification of Ellman's spectrophotometric method. Methods: Anti-acetylcholinesterase activity was evaluated by using a modification of Ellman's spectrophotometric method. The spectrophotometric method is based on the reaction of released thiocholine to give a coloured product with a chromogenic reagent 5,5-dithio-bis-(2-nitrobenzoic acid). Results: The anti-acetylcholinesterase effects of the compounds (1a-e, 2a-e, 3a-e and 4a-4e) were determined by modified Ellman's spectrophotometric method. Among these compounds, (4-{[(4-trifluoromethylphenyl)carbamoyl]amino}phenyl)acetic acid (1d), was found as the most active compound. The inhibition percentages were calculated 48.55% at 0.1 mM concentrations for compound 1d. Conclusion: The anti-acetylcholinesterase activity screening indicated that among the tested compounds, 1d bearing 4-trifluoromethyl group on the phenyl ring, showed noteworthy anti-acetylcholinesterase activity. Based on the activity results, it appears that halogen atoms on the phenyl ring have made good contribution to the anti-acetylcholinesterase activity.

A New Class of Linezolid‐Based Molecules as Potential Antimicrobial and Antitubercular Agents: A Rational Approach

“…[14] The divalent sulphur is characterized by its ability to interact with electron-poor as well as with electron-rich functional groups, which improves the binding ability of the molecule to receptors more efficiently. Drugs having urea/thiourea functionality are known to display anticonvulsant, [15] antimicrobial, [16] anti-trypanosomal, [17] antidepressant, [18] antiviral, [19] anti-acetylcholinesterase, [20] antiproliferative [21] and anti-inflammatory. [22] Furthermore, sulfone containing bioactive molecules have been reported to display several therapeutic activities, including antimicrobial, antifungal, antimalarial, anti-cancer, anti-HIV, anti-proliferative, enzyme inhibitors and anti-inflammatory activity.…”

Synthesis and cholinesterase inhibitory activity of some phenylacetamide derivatives bearing 1H-pyrazole and 1H-1,2,4-triazole

“…Donepezil, rivastigmine and galanthamine also carry heterocyclic rings and according to literature survey, most of the compounds that have exhibited Ache inhibition consists of heterocyclic ring systems including pyrazole and 1,2,4-triazole (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Besides Ache inhibitory activity, pyrazole and 1,2,4-triazole containing systems have a wide spectrum of biological activities such as antibacterial, antifungal, analgesic, antipyretic, antiinflammatory, antiviral, anticancer, antituberculosis, antiparasitic, antihyperglycemic, antidepression, antihypertensive, vasodilatory, anticonvulsant activity (5,9,10,(14)(15)(16).…”