Begüm EVRANOS AKSÖZ, Fatma KAYNAK ONURDAĞ, Erkan AKSÖZ, Selda ÖZGEN ÖZGACAR

Bazı hidrazon ve kalkon türevlerinin biyolojik aktivite taraması

Amaç: Günümüzde antibiyotiklere karşı direnç gelişimi hızla artmaktadır. Direnç gelişmesi nedeniyle antibiyotik etkinliğinin kaybı ciddi tehlikelere neden olmaktadır. Özellikle metisiline dirençli Staphylococcus aureus ve vankomisine dirençli Enterococcus faecalis izolatı, bağışıklık sistemi zayıf olan hastalarda yaşamı tehdit eden durumlar oluşturmaktadır. Bu nedenle, bu mikroorganizmalara karşı yeni ilaç etken maddeleri geliştirmek önemlidir. Bu makalede, hidrazonlar ve kalkonlar sentezlenmiş ve bu bileşiklerin antimikrobiyal ve antitüberküloz gibi bazı biyolojik aktivitelerinin araştırılması yapılmıştır. Bu çalışma, mevcut antibiyotiklere karşı hızla artan direnç nedeniyle etkinliğini kaybeden antibiyotiklerin yerine antimikrobiyal ve antitüberküloz etkili yeni ilaç etken maddelerinin araştırılması için yapılmıştır. Yöntem: Bileşikler, Claisen Schmidt kondensasyonu yoluyla kalkonların sentezi ve daha sonra bu kalkonların hidrazon oluşturmak üzere hidrazidlerle reaksiyona girmesiyle elde edilmiştir. Bileşiklerin antimikrobiyal ve antitüberküloz aktiviteleri, sırasıyla mikrodilüsyon yöntemi ve mikroplak alamar mavisi deneyleri ile değerlendirilmiştir. Bulgular: Tüm bileşikler Mycobacterium tuberculosis’e karşı aynı etkiyi göstermiştir (MİK: 64 ug/ mL). E4, 4’-Bromo-4-metil kalkon, metisiline dirençli- Staphylococcus aureus’a karşı en iyi etkinliği göstermiştir (MİK: 16 ug/mL). Enterococcus faecalis izolatı ve Enterococcus faecalis’e karşı en etkili bileşikler sırasıyla B26 (N-(1-(4-florofenil)-3-p-tolilaliliden)tiyofen-2- karbonhidrazit) ve E8 (4’-floro-3-metil kalkon) olarak bulunmuştur. Sonuç: Hidrazonların S. aureus ATCC 29213 suşu üzerine kalkonlardan daha etkili olduğu bulunmuştur. Bununla birlikte kalkonlar, metisiline dirençli- Staphylococcus aureus ve Enterococcus faecalis üzerine dikkate değer bir etki göstermiştir. Tüberküloz basili açısından, bileşiklerin kalkon veya hidrazon yapısında olması fark göstermemiştir. Hem kalkonlar hem de hidrazonlar kandida türlerine karşı aynı aktiviteyi sergilemiştir. Tüm bileşiklerin metisiline dirençli Staphylococcus aureus üzerine gentamisinden daha etkili olduğu gözlenmiştir.

Biological activity screening of some hydrazone and chalcone derivatives

Objective: Today, the development of resistance to antibiotics is increasing rapidly. Loss of antibiotics effectiveness due to the development of resistance causes serious hazards. Especially methicillinresistant Staphylococcus aureus and vancomycinresistant Enterococcus faecalis create life-threatening conditions in patients with a weak immune system. For this reason, it is important to develop new drug active substances against these microorganisms. In this article, hydrazones and chalcones were synthesized and some biological activities of these compounds such as antimicrobial and antituberculosis were investigated. This study was conducted to investigate new antimicrobial and antituberculous drug-active substances instead of antibiotics that lost their effectiveness due to the rapidly increasing resistance to existing antibiotics. Methods: The compounds were obtained by synthesis of chalcones via Claisen Schmidt condensation and then by reacting these chalcones with hydrazides to form hydrazone. Antimicrobial and antituberculosis activities of the compounds were evaluated by microdilution method and microplate alamar blue assays, respectively. Results: All compounds displayed the same activity against Mycobacterium tuberculosis (MIC: 64 μg/mL). E4, 4’-Bromo-4-methyl chalcone, displayed the best activity against Meticilline resistant-Staphylococcus aureus (MIC: 16 μg/mL). The most effective compounds against Enterococcus faecalis isolate and Enterococcus faecalis were found B26 (N-(1-(4fluorophenyl)-3-p-tolylallylidene) thiophene-2-carbohydrazide) and E8 (4’-fluoro-3-methyl chalcone), respectively (MIC: 32 μg/mL). Conclusion: Hydrazones have been found to be more effective than chalcones against S. aureus ATCC 29213. However, chalcones exhibited a remarkable effect against meticilline resistant-Staphylococcus aureus and Enterococcus faecalis. In terms of tuberculosis bacillus, it did not differ whether the compounds had a chalcone or hydrazone structure. Both chalcones and hydrazones exhibited the same activity against candida species. All compounds were observed to be more effective than gentamicin against methicillin-resistant Staphylococcus aureus.

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