Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents

Year 2015, Volume: 19 Issue: 2, 88 - 102, 10.04.2015

Esra Tatar , Şükriye Küçükgüzel , Sevgi Karakuş Eric De Clercq Graciela Andrei Robert Snoeck Christophe Pannecouque Sinem Öktem-okullu Nihal Ünübol Tanıl Kocagöz Sadık Kalaycı Fikrettin Şahin , İlkay Küçükgüzel

https://doi.org/10.12991/mpj.2015199639

Abstract

Some novel 1,3,4-thiadiazole [5-8] and 1,2,4-triazole [9-12] derivatives carrying amino acid moiety were synthesized starting from L-methionine. 1,3,4-Thiadiazole and 1,2,4-triazole scaffolds were prepared by cyclocondensation of the corresponding thiosemicarbazide and finally converted to their thiourea derivatives. Structures of the synthesized compounds [4-12] were confirmed by IR, 1H-NMR and 13C-NMR spectral data and elemental analysis. Synthesized compounds were evaluated for their antiviral and antibacterial activity. Of the screened compounds, N-{3-(methylsulfanyl)-1-[5-(phenylamino)-1,3,4-thiadiazole-2-yl]propyl}benzamide [5] was identified as the most potent inhibitor of Influenza A H3N2 virus with an EC50value of 31.4 μM, which serves as a lead compound for prospective development. The antituberculosis activity screen of the synthesized compounds revealed 1-[4-(4-chloro-(3-trifluoromethyl)phenyl-3-[3-(methylsulfanyl)-1-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)propyl]thiourea [12] as the most active compound against M. tuberculosis H37Rv strain (MIC : 16 µg/mL).

Keywords

Thioureas; 1, 3, 4-thiadiazoles; 1, 2, 4-triazoles; antiviral activity; influenza; antituberculosis activity

L-Metiyoninden hareketle elde edilen bazı yeni 1,3,4-tiyadiazol ve 1,2,4-triazol türevlerinin sentezi, antitüberküler ve antiviral etkilerinin değerlendirilmesi

Abstract

Bu çalışma kapsamında, L-metiyonin’den hareketle bazı yeni
1,3,4-tiyadiazol [5-8] ve 1,2,4-triazol [9-12] türevi bileşikler
sentezlenmiştir. İlgili tiyosemikarbazit’in siklokondensasyonu
ile elde edilen 1,3,4-tiyadiazol ve 1,2,4-triazol bileşikleri, yeni
tiyoüre türevlerinin sentez başlangıç maddelerini de
oluşturmaktadır. Sentezlenen bileşiklerin [4-12] yapıları IR,
1H-NMR ve 13C-NMR spektroskopisi yöntemleriyle
aydınlatılmıştır. Elde edilen bileşikler antiviral ve
antibakteriyel etkinlikleri açısından değerlendirilmişlerdir.
N-{3-(Metilsülfanil)-1-[5-(fenilamino)-1,3,4-tiyadiazol-2-il]
propil}benzamit’in [5], Influenza A H3N2 virüsüne karşı EC50:
31.4 μM derişimde etkinlik gösterdiği saptanmış ve devam
eden çalışmalarda geliştirilmek üzere önder bileşik olarak
tanımlanmıştır. Antitüberküloz etki çalışmaları sonucunda
1-[4-(4-kloro-(3-trifluorometil)fenil]-3-[3-(metilsülfanil)-1-(4-
fenil-5-tiyokso-4,5-dihidro-1H-1,2,4-triazol-3-il)propil]
tiyoüre’nin [12] M. tuberculosis H37Rv suşuna karşı MİK :
30.88 µM derişimde etkinlik gösterdiği belirlenmiştir.

Keywords

Tiyoüre, 1, 3, 4-tiyadiazol, 1, 2, 4-triazol, antiviral etki, influenza, antitüberküler etki

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