Abstract
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.
Highlights
Due to the multiple advantages of natural products (Atanasov et al, 2021), modern medicine still depends on them and their molecules for the development of new drugs, being the area of the anti-infectives and anti-cancers where there is a more marked influence (Newman and Cragg, 2020; Luo et al, 2021)
The fraction eluted with chloroform (34S-F02) had the highest yield and the highest antibacterial activity against S. aureus strains (ATCC 29213, ATCC 33591, ATCC 43300 and USA300-0114), which, together with the fraction eluted with ethyl acetate, accounted for approximately 90% of the extract content, so it could be considered that components of the extract are mostly of medium polarity
The Nuclear Magnetic Resonance (NMR) spectrum of the compound at 25.3 min indicated the structure of a mammea coumarin called mammea B/BC (5 mg) while the peak at 35 min corresponded to mammea B/BA (6 mg)
Summary
Due to the multiple advantages of natural products (Atanasov et al, 2021), modern medicine still depends on them and their molecules for the development of new drugs, being the area of the anti-infectives and anti-cancers where there is a more marked influence (Newman and Cragg, 2020; Luo et al, 2021). It is preferable to have broad-spectrum antibiotics (Cheung et al, 2021), the isolation of active molecules against Gram-positive bacteria remains a laudable alternative because one of the microorganisms of greatest concern due to the lack of new antibiotics continues to be S. aureus. This organism is the major cause of uncomplicated skin infections and serious invasive infections worldwide due to its numerous toxins, immune evasion factors, and its resistance to almost all available antibiotics. In the US, mortality from MRSA remains the highest for any antibiotic-resistant pathogen (Cheung et al, 2021)
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