Bazı yeni imidazo [2,1-b][1,3,4]tiyadiazol türevlerinin sentezi ve biyolojik aktivitelerinin incelenmesi
Küçük Resim Yok
Tarih
2017
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Karabük Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Bu çalışmanın amacı, imidazo[2,1-b][1,3,4]tiyadiazol türevlerini sentezlemek, çeşitli spektroskopik yöntemlerle karakterize etmek ve antifungal aktivitelerinin araştırmaktır. 2-amino-1,3,4-tiyadiazol türevleri (2a,b) nitril bileşikleri (1a,b) yüzde 75 ve 88 oranlarında tiyosemikarbazitle reaksiyona girerek sentezlenmiştir. Daha sonra hedef bileşikler olan imidazo[2,1-b][1,3,4]tiyadiazol türevler (4-21), 2-amino-1,3,4-tiyadiazol türevlerinin 2a,b fenasil bromür türevleri ile (3a-i) olan reaksiyonlarından % 52-69 oranlarında sentezlendi. Tüm sentezlenen bileşiklerin yapıları, IR, 1H-NMR, 13C-NMR, elemental analiz ve kütle spektroskopisi ile karakterize edildi ve ayrıca X-Ray kırılma analizi 7, 8, 10, 17 bileşikleri için kullanıldı. Ardından, tüm sentezlenen bileşiklerin in vitro ortamda antifungal aktivitelerine bakıldı. İnhibisyon alanları, inhibisyon yüzdeleri ve LD50 dozları belirlendi. Sentezlenen bileşiklerin çoğu, bitki patojenlerine karşı iyi antifungal aktiviteler sergiledi. Moleküler doking ve elektronik özellik hesaplamaları, ligandların olası bağlanma konformasyonları ve sübstitüentlerin aktiviteler üzerindeki etkilerini görmek için uygulandı. Doking puanı, en düşük oktanol / su dağılım katsayısı ve yüksek HOMO enerji değerine sahip olduğu bulunan en aktif bileşik olan 10'nun aktivitesini başarılı bir şekilde yansıtmaktadır. Deneysel ve hesaplamalı çalışmaların birleştirilmesi, tüm bileşiklerin umut verici aktiviteleri olduğu ve yeni ilaç adayı olabileceklerini göstermiştir.
The aim of this study was to synthesize imidazo[2,1?b][1,3,4]thiadiazole derivatives, characterize them with various spectroscopic methods and investigate their antifungal activities. 2?amino?1,3,4?thiadiazole derivatives 2a,b were synthesized by reacting nitrile compounds 1a,b with thiosemicarbazide (yields 75% and 88%). We then synthesized imidazo[2,1?b][1,3,4]thiadiazole derivatives 4?21, the target compounds, from the reactions of 2?amino?1,3,4?thiadiazole derivatives 2a,b with phenacyl bromide derivatives 3 (yields 52?69%). The structures of all synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectroscopy and X?ray diffraction analysis was also used for the compounds 7, 8, 10 and 17. Subsequently, in vitro antifungal activity tests were applied to all synthesized compounds. Inhibition zones, percentages of inhibition and LD50 doses were determined. Most of the synthesized compounds exhibited good antifungal activity against plant pathogens. Molecular docking and electronic properties calculations were carried out in order to see the potential binding conformations of the ligands and the effect of the substituents on the activities. Docking score successfully reflects the activity of the most active compound 10 which was found to have the lowest octanol/water partition coefficient and high HOMO energy value. The combination of experimental and computational work show that all the synthesized compounds have promising activities and might serve as novel drug candidates.
The aim of this study was to synthesize imidazo[2,1?b][1,3,4]thiadiazole derivatives, characterize them with various spectroscopic methods and investigate their antifungal activities. 2?amino?1,3,4?thiadiazole derivatives 2a,b were synthesized by reacting nitrile compounds 1a,b with thiosemicarbazide (yields 75% and 88%). We then synthesized imidazo[2,1?b][1,3,4]thiadiazole derivatives 4?21, the target compounds, from the reactions of 2?amino?1,3,4?thiadiazole derivatives 2a,b with phenacyl bromide derivatives 3 (yields 52?69%). The structures of all synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectroscopy and X?ray diffraction analysis was also used for the compounds 7, 8, 10 and 17. Subsequently, in vitro antifungal activity tests were applied to all synthesized compounds. Inhibition zones, percentages of inhibition and LD50 doses were determined. Most of the synthesized compounds exhibited good antifungal activity against plant pathogens. Molecular docking and electronic properties calculations were carried out in order to see the potential binding conformations of the ligands and the effect of the substituents on the activities. Docking score successfully reflects the activity of the most active compound 10 which was found to have the lowest octanol/water partition coefficient and high HOMO energy value. The combination of experimental and computational work show that all the synthesized compounds have promising activities and might serve as novel drug candidates.
Açıklama
Fen Bilimleri Enstitüsü, Kimya Ana Bilim Dalı
Anahtar Kelimeler
Biyoteknoloji, Biotechnology ; Kimya
