Publication: Etofenamat’tan hareketle 1,4-disübstitüe tiyosemikarbazidler ve sübstitüe 1,2,4-triazol türevlerinin sentezi ve biyolojik aktiviteleri üzerine çalışmalar
Abstract
Amaç: Bu tez çalışmasında nonstreroidal antienflamatuvar ilaç etkin maddesi olan Etofenomat’ tan hareketle alkil/ aril-1,4-disübstitüe tiyosemikarbazidlerin ve alkil/ arilsübstitüe-1,2,4-triazol-3-tiyonların sentez edilmesi amaçlanmıştır. Gereç ve Yöntem: Tez kapsamında etofenamat etkin maddesinden hareketle 2-(3-(triflorometil)fenilamino)benzohidrazit (1) elde edilmiş; 1’in metil/ propil/ fenetil/ allil/ siklohegzil/ benzoil/ fenil/ 2-florofenil/ 3-florofenil/ 4-metoksifenil ve 4-triflorometoksifenil isotiyosiyanatlara katımı ile N-alkil/ aril-2-(2-{[3-(triflorometil)fenil] amino}benzoil)hidrazinkarbotiyoamidler (2a-k) ve 2a-k’nin 2N NaOH ile siklizasyonundan 4-alkil/ aril-5-(2-{[3-(triflorometil)fenil]amino}fenil)-2,4-dihidro-3H-1,2,4-triazol-3-tiyon (3a-k)’ler sentez edilmiştir. Bulgular: Moleküllerin saflıkları elementel analiz ile tayin edilmiş, IR, 1H-NMR ve kütle spektrumları alınmıştır. Sonuç: Sentez edilen tüm bileşiklerin sitotoksisite taraması MTT yöntemiyle yapılmıştır. Sitotoksisite araştırması sonucunda özellikle metil sübstitüentli triazol türevi olan 3a bileşiği 5.0 μg/ mL konsantrasyonda hücre proliferasyonunu arttırıcı etki göstermiş (% 101,89) ve artan konsantrasyonda (10 μg/ mL) % 8,40 büyüme inhibisyon değeri ile en düşük büyüme inhibisyon ve en yüksek % canlılık değerine (% 91,60) sahip sentez bileşiği olmuştur. En düşük büyüme inhibisyon değerleri 5,0 μg/ mL konsantrasyonda % 0 ile 3a, % 1,84 ile 2-florofenil sübstitüentlitiyosemikarbazid olan 2h ve % 2,64 ile 2-florofenil sübstitüentli triazol olan 3h sentez bileşiklerinde elde edilmiştir. En yüksek büyüme inhibisyon değeri ise 10μg/ mL konsantrasyonda % 52,96 ile siklohegzil sübstitüentlitiyosemikarbazid olan 2e, % 47,41 ile benzoil sübstitüentlitiyosemikarbazid 2f ve % 39,26 ile 4-metoksifenil sübstitüentlitiyosemikarbazid 2j bileşiklerinde elde edilmiştir. 2e bileşiği ile 10 μg/ mL konsantrasyonda elde edilen % 52,96 büyüme inhibisyon değeri % 50’nin üzerinde olduğu için 2e bileşiği 10 μg/ mL konsantrasyonda sitotoksik olarak gözlemlenmiştir.
Objective: In this thesis, it was aimed to synthesize alkyl/ aryl-1,4-disubstitued thiosemicarbazides and alkyl/ arylsubstituted-1,2,4-triazole-3-thiones based on Etofenomat which is a non-steroidal anti-inflammatory drug. Materials and Methods: Within the scope of the thesis, 2-(3-(trifluoromethyl)phenylamino)benzohydrazide (1) was obtained from etophenamat; N-alkyl/ aryl-2-(2-{[3-(trifluoromethyl)phenyl]amino}benzoyl) hydrazine carbothioamide (2a-k) were synthesized by adding 1 to methyl/ propyl/ phenethyl/ allyl/ cyclohexyl/ benzoyl/ phenyl/ 2-fluorophenyl/ 3-fluorophenyl/ 4-methoxyphenyl and 4-trifluoromethoxyphenyl isothiocyanates; 4-alkyl/ aryl-5-(2-{[3-(trifluoromethyl)phenyl]amino}phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-thiones (3a-k) were synthesized as a result of cyclization of 2a-k with 2N NaOH. Results: Purities of the compounds were determined by elemental analysis, IR, 1H-NMR and mass spectra were evaluated. Conclusion: Cytotoxicity screening of all compounds was performed by MTT method. As a result of cytotoxicity research, especially 3a showed an increasing effect on cell proliferation at 5.0 μg/ mL concentration (101.89 %). It was observed that 3a showed the lowest growth inhibition with 8.40% and highest viability with 91.60 % at the increasing concentration (10 μg/ mL) was the synthesis compound. The lowest growth inhibition values were obtained from compound 3a, 2h and 3h with 0.0 %, 1.84 % and 2.64 % at 5.0 μg/ mL concentration, respectively. The highest growth inhibition value was obtained from cyclohexyl substituted thiosemicarbazide 2e, 2f and 2j with 52.96 %, 47.41 % and 39.26 % at at 10 μg/ mL concentration, respectively. Since the 52.96 % growth inhibition value obtained with 2e at a concentration of 10 μg/ mL was above 50.00 %, 2e was observed to be cytotoxic at a concentration of 10 μg/ mL.
Objective: In this thesis, it was aimed to synthesize alkyl/ aryl-1,4-disubstitued thiosemicarbazides and alkyl/ arylsubstituted-1,2,4-triazole-3-thiones based on Etofenomat which is a non-steroidal anti-inflammatory drug. Materials and Methods: Within the scope of the thesis, 2-(3-(trifluoromethyl)phenylamino)benzohydrazide (1) was obtained from etophenamat; N-alkyl/ aryl-2-(2-{[3-(trifluoromethyl)phenyl]amino}benzoyl) hydrazine carbothioamide (2a-k) were synthesized by adding 1 to methyl/ propyl/ phenethyl/ allyl/ cyclohexyl/ benzoyl/ phenyl/ 2-fluorophenyl/ 3-fluorophenyl/ 4-methoxyphenyl and 4-trifluoromethoxyphenyl isothiocyanates; 4-alkyl/ aryl-5-(2-{[3-(trifluoromethyl)phenyl]amino}phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-thiones (3a-k) were synthesized as a result of cyclization of 2a-k with 2N NaOH. Results: Purities of the compounds were determined by elemental analysis, IR, 1H-NMR and mass spectra were evaluated. Conclusion: Cytotoxicity screening of all compounds was performed by MTT method. As a result of cytotoxicity research, especially 3a showed an increasing effect on cell proliferation at 5.0 μg/ mL concentration (101.89 %). It was observed that 3a showed the lowest growth inhibition with 8.40% and highest viability with 91.60 % at the increasing concentration (10 μg/ mL) was the synthesis compound. The lowest growth inhibition values were obtained from compound 3a, 2h and 3h with 0.0 %, 1.84 % and 2.64 % at 5.0 μg/ mL concentration, respectively. The highest growth inhibition value was obtained from cyclohexyl substituted thiosemicarbazide 2e, 2f and 2j with 52.96 %, 47.41 % and 39.26 % at at 10 μg/ mL concentration, respectively. Since the 52.96 % growth inhibition value obtained with 2e at a concentration of 10 μg/ mL was above 50.00 %, 2e was observed to be cytotoxic at a concentration of 10 μg/ mL.