ANTİMİKROBİYAL AJAN OLARAK YENİ SÜLFONAMIDO-BENZOKSAZOL TÜREVLERİ: TASARIM, SENTEZ VE BİYOLOJİK DEĞERLENDİRME

Year 2024, Volume: 48 Issue: 1, 150 - 157, 20.01.2024

Meryem Erol , Cemre Acar-halıcı , Gülcan Kuyucuklu , Alparslan Semih Salan , Özlem Temiz-arpacı

https://doi.org/10.33483/jfpau.1341483

Abstract

Amaç: Bulaşıcı hastalıklarla mücadelede yeni ilaç-etkin madde aday bileşikleri geliştirmek ve öncü bileşiklere ulaşmak için birçok araştırma yapılmaktadır. Bu çalışmanın amacı, genel yapısı 2-(4-tert-bütilfenil)-5-(4-sübstitüefenilsülfonamido)benzoksazol olan altısı yeni olmak üzere toplam yedi bileşiğin yapılarını aydınlatmak ve mikrodilüsyon yöntemini kullanarak antimikrobiyal aktivitelerini test etmektir.
Gereç ve Yöntem: Bileşiklerin sentezi iki aşamada gerçekleştirilmiştir. İlk basamakta, PPA katalizörü altında 2,4-diaminofenol ve 4-tert-bütilbenzoik asit refluks edilmiş ve ikinci aşamada 4-sübstitüebenzensülfonil klorürün 5-Amino-2-(4-tert-bütilfenilbenzoksazol ile reaksiyona sokulmasıyla hedef bileşikler üretilmiştir. Bileşiklerin antimikrobiyal aktivitesi, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans ve bu mikroorganizmaların ilaca dirençli suşları kullanılarak in vitro antimikrobiyal aktivite çalışmaları ile belirlenmiştir. Ayrıca, SwissADME çevrimiçi yazılımı kullanılarak tahmini ADME profilleri hesaplanmıştır.
Sonuç ve Tartışma: Sentezlenen bileşiklerin yapıları, 1H-NMR, 13C-NMR ve Kütle spektroskopisi kullanılarak aydınlatıldı ve ayrıca erime noktaları belirlenmiştir. Bileşiklerin antimikrobiyal aktiviteleri 64 µg/ml ila ˃512 µg/ml aralığındaydı ve referans ilaçlardan daha zayıftı. En iyi antimikrobiyal aktivite, tüm bileşiklerin 64 µg/ml MİK değerlerine sahip olduğu bir E. faecalis izolatına karşı rapor edilmiştir. Sentezlenen yedi bileşikten altısının yeni olması ve antibakteriyel aktivitelerinin ilk kez test edilecek olması, yeni veya alternatif antimikrobiyal ajanların geliştirilmesine yönelik çalışmalara önemli katkı sağlayacaktır.

Keywords

ADME, antimikrobiyal aktivite, benzoksazol, sülfonamid

NEW SULFONAMIDO-BENZOXAZOLE DERIVATIVES AS ANTIMICROBIAL AGENTS: DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION

Abstract

Objective: Many investigations are conducted in the battle against infectious diseases in order to develop new drug-active ingredient candidate compounds and to identify leading compounds. The goal of this study was to synthesis a total of seven compounds, six of which are novel, with the general structure 2-(4-tert-butylphenyl)-5-(4-substitutedphenylsulfonamido)benzoxazole, to elucidate their structures, and to test their antimicrobial activities using the microdilution method.
Material and Method: The synthesis of the compounds was carried out in two stages. In the first stage, under PPA catalyst 2,4-diaminophenol and 4-tert-butylbenzoic acid were refluxed, and target compounds were produced in the second step by reacting 4-substitutedbenzenesulfonyl chloride with 5-Amino-2-(4-tert-butylphenyl)benzoxazole. The compounds' antimicrobial activity was determined by using Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and drug-resistant strains of these microorganisms in vitro antimicrobial activity studies. Furthermore, estimated ADME profiles were calculated using the SwissADME online software.
Result and Discussion: The structures of the synthesized compounds were elucidated using 1H-NMR, 13C-NMR and Mass spectroscopy, and also their melting points were determined. The antimicrobial activities of the compounds ranged from 64 µg/ml to ˃512 µg/ml and were weaker than the reference drugs. The best antimicrobial activity was reported against an isolate of E. faecalis, with all compounds having MIC values of 64 µg/ml. The fact that six of the seven synthesized compounds are novel and that their antimicrobial activity will be tested for the first time will make a significant contribution to studies to develop new or alternative antimicrobial agents.

Keywords

ADME, antimicrobial activity, benzoxazole, sulfonamide

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