Maggio Benedetta, Raffa Demetrio, Raimondi Maria Valeria, Cascioferro Stella, Plescia Fabiana, Schillaci Domenico, Cusimano Maria Grazia, Leonchiks Ainars, Zhulenkovs Dmitrijs, Basile Livia, Daidone Giuseppe
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, I-90123 Palermo, Italy.
IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia, Via Emerico Amari 123, I-90139 Palermo, Italy.
Molecules. 2016 Feb 19;21(2):241. doi: 10.3390/molecules21020241.
A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenyl)hydrazinylidene)butanoic acid (2b), showing an IC50 value of 50 µM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compound resulted 2a, which showed inhibition of about 60% against S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538 and S. epidermidis RP62A at a screening concentration of 100 µM.
一种基于荧光共振能量转移（FRET）的随机筛选测定法被用于生成作为分选酶A抑制剂的命中化合物，这使我们能够鉴定出3-氧代-2-(2-苯基亚肼基)丁酸乙酯作为一类新型分选酶A抑制剂的一个实例。通过将乙氧羰基官能团换成羧基、氰基或酰胺基，或者在酯和酸衍生物的苯环中引入取代基，生成了其他类似物。发现的最具活性的衍生物是3-氧代-2-(2-(3,4-二氯苯基)亚肼基)丁酸（2b），其IC50值为50 μM。为了对它们的抗毒力特性进行初步评估，对新衍生物的抗生物膜活性进行了测试。最具活性的化合物是2a，在100 μM的筛选浓度下，它对金黄色葡萄球菌ATCC 29213、金黄色葡萄球菌ATCC 25923、金黄色葡萄球菌ATCC 6538和表皮葡萄球菌RP62A表现出约60%的抑制率。
