Phan Phuong-Thuy T, Nguyen Thu-Trang T, Nguyen Hong-Nhung T, Le Bao-Khanh N, Vu Thao T, Tran Dong C, Pham Tuan-Anh N
Department of Medicinal Chemistry, Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam.
Department of Pharmaceutics, Faculty of Pharmacy, Da Nang University of Medical Technology and Pharmacy, Da Nang 550000, Vietnam.
Molecules. 2017 Apr 25;22(5):687. doi: 10.3390/molecules22050687.
In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive (MSSA) ATCC 29213, methicillin-resistant (MRSA) ATCC 43300, and () ATCC 29212) and one Gram-(-) strain ( ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap-Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse -ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including , MSSA and MRSA with the most potent antibacterial agent (MICs = 0.06-0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM () and 0.12 mM (). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.
为了发现新型抗菌剂，设计、合成了一系列2-水杨酰基苯并呋喃衍生物，并对其针对三种革兰氏阳性菌株（甲氧西林敏感金黄色葡萄球菌（MSSA）ATCC 29213、耐甲氧西林金黄色葡萄球菌（MRSA）ATCC 43300和粪肠球菌ATCC 29212）和一种革兰氏阴性菌株（大肠杆菌ATCC 25922）的抗菌活性进行了评估。2-水杨酰基苯并呋喃杂环通过水杨醛与苯甲酰溴的Rap-Stoermer缩合反应生成，然后通过威廉姆森合成法转化为多种醚衍生物。通过琼脂孔扩散法和琼脂稀释法对目标产物进行体外定性（抑菌圈）和定量（MIC）抗菌活性筛选。在这些化合物中，发现带有羧酸官能团的化合物对革兰氏阳性细菌菌株包括粪肠球菌、MSSA和MRSA表现出合理的活性，其中最有效的抗菌剂MICs = 0.06 - 0.12 mM。此外，2-水杨酰基苯并呋喃对MRSA部分表现出抑制活性，最佳MICs分别为0.14 mM（粪肠球菌）和0.12 mM（MSSA）。最后，抗菌结果初步表明，在水杨酰基-C2处带有羧酸基团的取代基以及苯并呋喃部分上的溴原子似乎是抗菌活性所必需的官能团。
