Postgraduate Institute of Science, University of Peradeniya, Sri Lanka; Department of Biochemistry, Medical Research Institute, Colombo, Srilanka.
Department of Chemistry, Faculty of Science, University of Peradeniya, Sri Lanka.
Bioorg Med Chem. 2021 May 15;38:116142. doi: 10.1016/j.bmc.2021.116142. Epub 2021 Apr 2.
Multi- drug resistant microbial pathogens are a serious global health problem and thus new antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. Hence, the objective of the present study was to investigate the antibacterial activity of 6β-hydroxy-3-oxolup-20(29)-en-28-oic acid (6β-hydroxy betunolic acid) isolated from the bark of Schumacheria castaneifolia and its effect when combined with oxacillin. Antibacterial potential of 6β-hydroxy betunolic acid alone was performed using broth micro dilution assay against sixteen bacterial strains which included eight standard strains [Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), carbapenemase producing Kebsiella pneumonia (ATCC BAA 1705), carbapenemase non-producing K. pneumonia (ATCC BAA 1706) and Pseudomonas aeruginosa (ATCC 27853)] and four strains each of clinically isolated meropenem resistant Acinetobactor sp. and methicillin resistant S. aureus (MRSA) which were included in the urgent threat list and serious threat list, respectively in 2019 by the Centers for Disease Control and Prevention in the United States. Its effect when combined with oxacillin was tested against S. aureus (ATCC 29213) and MRSAs using a checkerboard dilution method. The results indicated that 6β-hydroxy betunolic acid had antibacterial activity against the tested Gram positive organisms with MICs ranging from 16 to 32 mg L (MIC of oxacillin and meropenem ranged from 0.25-16 and 0.03-128 mg L respectively). The high MIC values (>1024 mg L) of 6β-hydroxy betunolic acid against Gram negative strains indicated a likely lack of activity. Further, 6β-hydroxy betunolic acid exhibited synergistic effect with oxacillin against Staphylococcus aureus (0.49) and showed an additive effect against all the tested MRSAs. The present study suggested that the antibacterial activity of the 6β-hydroxy betunolic acid is restricted to Staphylococcus isolates and possibly Enterococcus faecalis. Further testing on different types of Gram positives and identification of the exact mechanism of action would be of importance.
多药耐药微生物病原体是一个严重的全球健康问题，因此迫切需要新的抗菌药物，这些药物单独使用和与传统抗生素联合使用都具有疗效。因此，本研究的目的是研究从 Schumacheria castaneifolia 树皮中分离得到的 6β-羟基-3-氧代-30(29)-羊毛甾-28-酸（6β-羟基白桦脂酸）的抗菌活性及其与苯唑西林联合使用的效果。单独使用 6β-羟基白桦脂酸的抗菌潜力通过肉汤微量稀释法对 16 株细菌菌株进行了测试，其中包括 8 株标准菌株[金黄色葡萄球菌（ATCC 29213 和 ATCC 25923）、粪肠球菌（ATCC 29212）、大肠杆菌（ATCC 35218 和 ATCC 25922）、产碳青霉烯酶肺炎克雷伯菌（ATCC BAA 1705）、不产碳青霉烯酶肺炎克雷伯菌（ATCC BAA 1706）和铜绿假单胞菌（ATCC 27853）]和临床分离的耐美罗培南不动杆菌各 4 株和耐甲氧西林金黄色葡萄球菌（MRSA）各 4 株，分别列入美国疾病控制与预防中心 2019 年的紧急威胁清单和严重威胁清单。使用棋盘稀释法测试了其与苯唑西林联合使用对金黄色葡萄球菌（ATCC 29213）和耐甲氧西林金黄色葡萄球菌的作用。结果表明，6β-羟基白桦脂酸对测试的革兰氏阳性菌具有抗菌活性，MIC 范围为 16-32mg/L（苯唑西林和美罗培南的 MIC 范围分别为 0.25-16 和 0.03-128mg/L）。6β-羟基白桦脂酸对革兰氏阴性菌的高 MIC 值（>1024mg/L）表明其可能缺乏活性。此外，6β-羟基白桦脂酸与苯唑西林联合使用对金黄色葡萄球菌表现出协同作用（0.49），并对所有测试的耐甲氧西林金黄色葡萄球菌表现出相加作用。本研究表明，6β-羟基白桦脂酸的抗菌活性仅限于金黄色葡萄球菌分离株，可能还有粪肠球菌。进一步测试不同类型的革兰氏阳性菌并确定确切的作用机制将非常重要。
