İmidazo[2,1-b]tiyazol türevi heterosiklik bileşikler
Imidazo[2,1-b]thiazole derived heterocyclic compounds
Yazar: BERİN KARAMAN
Danışman: PROF. DR. NURAY ULUSOY GÜZELDEMİRCİ
İstanbul Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Kimya Ana Bilim Dalı
Derece: Yüksek Lisans, 2010
Konu: Eczacılık ve Farmakoloji = Pharmacy and Pharmacology
Dizin: Antineoplastik ajanlar = Antineoplastic agents ; Antitüberküloz ajanlar = Antitubercular agents ; Antiviral ajanlar = Antiviral agents ; Aril bileşikleri = Aryl compounds ; Tiyazoller = Thiazoles ; İmidazoller = Imidazoles

Özet:
Bu çalışmada, imidazo[2,1-b]tiyazol artığı taşıyan on yeni bileşik; [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid benzilidenhidrazid (1), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 2-hidroksibenziliden hidrazid (2), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 4-hidroksibenziliden hidrazid (3), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 4-metoksibenziliden hidrazid (4), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 4-nitrobenzilidenhidrazid (5), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 4-dimetilaminobenziliden hidrazid (6), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 3-metoksi-4-hidroksi benzilidenhidrazid (7), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 2,5-dimetoksibenziliden hidrazid (8), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 2,4-diklorobenziliden hidrazid (9), [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid 5-nitro-2-furfuriliden hidrazid (10) sentez edildi. Bu amaçla, ?-bromo-4-kloroasetofenon ve etil 2-aminotiyazol-4-asetat'ın reaksiyonu ile elde edilen 2-amino-3-[(4-klorobenzoil)metil]-4-(etoksikarbonilmetil)tiyazolyum bromür (A)'den absolü etanollü ortamda etil [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetat hidrobromür (B) kazanılmış, daha sonra (B), hidrazin hidrat ile etkileştirilerek [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid hidrazid (C) elde edilmiş, (C)'nin de çeşitli aromatik aldehidlerle kondensasyonundan literatürde yer almayan [6-(4-klorofenil)imidazo[2,1-b]tiyazol-3-il]asetik asid arilidenhidrazid yapısında on yeni bileşik (1-10) kazanılmıştır. Bileşiklerin yapıları elementel analiz ve spektral (UV, IR, 1H-NMR, 13C-NMR (APT, DEPT), HSQC ve ESI-MS) verilerle doğrulanmıştır. Bileşik 1-10 antibakteriyel ve antiviral aktivite, bileşik 2-10 antitüberküler aktivite açısından değerlendirilmişlerdir. Bileşiklerin hiçbirinde önemli bir antibakteriyel ve antitüberküler aktivite saptanamamıştır. Bileşik 3 ve 7'nin Herpes simplex virus-1 ve Vaksinia virus'lerine, bileşik 9'un ise Feline korona virus'e karşı aktif oldukları saptanmıştır. Bileşik 2 ve 8 antikanser aktivite taraması için seçilmiş ve bazı kanser hücrelerine karşı bir miktar inhibisyon gösterdikleri saptanmıştır.Anahtar Kelimeler: İmidazo[2,1-b]tiyazol, arilidenhidrazid, antitüberküler aktivite, antiviral aktivite, antikanser aktivite.Bu çalışma, İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir. Proje No: T-3731

Abstract:
In this study, ten new compounds bearing an imidazo[2,1-b]thiazole moiety; [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid benzylidenhydrazide (1), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 2-hydroxybenzyliden hydrazide (2), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 4-hydroxybenzyliden hydrazide (3), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 4-methoxy benzyliden hydrazide (4), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 4-nitrobenzyliden hydrazide (5), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 4-dimethylamino benzylidenhydrazide (6), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 3-methoxy-4-hydroxy benzylidenhydrazide (7), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 2,5-dimethoxy benzylidenhydrazide (8), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 2,4-dichlorobenzyliden hydrazide (9), [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid 5-nitro-2-furfuryliden hydrazide (10) were synthesized. Thus 2-amino-3-[(4-chlorobenzoyl)methyl]-4-(ethoxycarbonylmethyl)thiazolium bromide (A), obtained from the reaction of ethyl 2-aminothiazol-4-acetate with ?-bromo-4-chloroacetophenon was reacted with absolute ethanol to yield ethyl [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetate hydrobromide (B). B was reacted with hydrazine hydrate to afford [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid hydrazide (C). By condensation of (C) with various aromatic aldehydes, ten new compounds (1-10) were obtained. The structures of the compounds were confirmed by elemental analysis and spectral (UV, IR, 1H-NMR, 13C-NMR (APT, DEPT), HSQC and ESI-MS) data. Compounds 1-10 were evaluated for antibacterial and antiviral activity and compounds 2-10 for antitubercular activity. None of the compounds exhibited significant antibacterial and antitubercular activity. Compounds 3 and 7 were found to be active against Herpes simplex virus-1 ve Vaccinia virus, and compound 9 against Feline corona virus. Compounds 2 and 8 were selected for anticancer activity screening and it was determined that they both showed some inhibition against some cancer cells.Key Words: Imidazo[2,1-b]thiazole, arylidenhydrazide, antitubercular activity, antiviral activity, anticancer activity.The present work was supported by the Research Fund of Istanbul University. Project No. T-3731