DataSheet1_Mammea B/BA Isolated From the Seeds of Mammea americana L. (Calophyllaceae) is a Potent Inhibitor of Methicillin-Resistant Staphylococcus aureus.docx

Staphylococcus aureus remains a pathogen of high concern in public health programs worldwide due to antibiotic resistance and emergence of highly virulent strains. Many phytochemicals have demonstrated activity against S. aureus and other Gram-positive bacteria, but the minimum inhibitory concentration (MIC) values comparable to commonly used antibiotics are needed. In the present study, bio-guided fractionation of the ethanol extract of seeds of Mammea americana L. (Calophyllaceae) throughout the antibacterial activity, against S. aureus strains that are sensitive and resistant to methicillin, led to the isolation of four coumarins identified as mammea B/BA, mammea B/BC, mammea A/AA cyclo D and mammea A/AA cyclo F, and a mixture of mammea B/BA cyclo F plus mammea B/BD cyclo F. The extract inhibited the growth of S. aureus with MIC values of 2–4 μg/ml and Mammea B/BA (MaBBA) presented MIC values in a range between 0.5 and 1.0 μg/ml in six methicillin-sensitive strains and eight methicillin-resistant strains evaluated. We consider MaBBA the most potent of all mammea coumarins reported to date, according to the literature review carried out at the time of writing of this article. Toxicity assessment in vivo against the nematode Caenorhabditis elegans and in vitro against human fibroblasts of the extract and the compound MaBBA indicated that both had low toxicity.

金黄色葡萄球菌（Staphylococcus aureus）因抗生素耐药性及高毒力菌株的出现，仍是全球公共卫生防控领域高度关注的病原菌。诸多植物化学成分已被证实对金黄色葡萄球菌及其他革兰氏阳性菌具有抗菌活性，但仍需获得与常用抗生素相当的最低抑菌浓度（minimum inhibitory concentration, MIC）数值。本研究以针对甲氧西林敏感与耐药金黄色葡萄球菌菌株的抗菌活性为导向，对南美琼崖海棠（Mammea americana L.，红厚壳科Calophyllaceae）种子的乙醇提取物开展生物导向分级分离，最终分离得到4种香豆素类化合物，分别鉴定为mammea B/BA、mammea B/BC、mammea A/AA cyclo D及mammea A/AA cyclo F，以及一组由mammea B/BA cyclo F与mammea B/BD cyclo F组成的混合物。该提取物对金黄色葡萄球菌的MIC值为2~4 μg/ml，而mammea B/BA（MaBBA）在受试的6株甲氧西林敏感菌株与8株甲氧西林耐药菌株中，MIC值介于0.5~1.0 μg/ml之间。结合本文撰写时开展的文献调研，研究团队认为MaBBA是目前已报道的所有mammea类香豆素中抗菌活性最强的化合物。此外，分别针对秀丽隐杆线虫（Caenorhabditis elegans）开展体内毒性评估、针对人成纤维细胞开展体外毒性评估，结果显示该提取物与MaBBA均具有较低的毒性。