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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #383020
Research Project: Discovery and Development of Natural Products for Pharmaceutical and Agrichemical Applications II

Location: Natural Products Utilization Research

Title: Schottiin, a new prenylated isoflavones from Psorothamnus schottii and antibacterial synergism studies between methicillin and fremontone against methicillin-resistant Staphylococcus aureus ATCC 1708

Author
item KUMAIRHAMY, MALIKA - University Of Mississippi
item ILIAS, MUHAMMAD - University Of Mississippi
item SIDDHARTH, TRIPATHI - University Of Mississippi
item SHABANA, KHAN - University Of Mississippi

Submitted to: Natural Product Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/25/2021
Publication Date: 6/14/2021
Citation: Kumairhamy, M., Ilias, M., Siddharth, T.K., Shabana, K. 2021. Schottiin, a new prenylated isoflavones from Psorothamnus schottii and antibacterial synergism studies between methicillin and fremontone against methicillin-resistant Staphylococcus aureus ATCC 1708. Natural Product Research. https://doi.org/10.1080/14786419.2021.1937157.
DOI: https://doi.org/10.1080/14786419.2021.1937157

Interpretive Summary: Psorothamnus schottii, previously known as Dalea schottii (Fabaceae), is one of the largest members of the genus Psoromanthus. Plants from this genus have been widely used by native American Apache and Dakotas tribes for various remedies, including headache, rheumatism, heart diseases, pneumonia, and also to treat stomach ailments. Prenylated flavonoids appear to be the potential chemotaxonomic markers of species from this genus and relevance to its reported ethnobotanical and ethnopharmacological properties. The current therapeutic options for the treatment of bacterial diseases are limited due to emergence of drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE), indicating an urgent need for new antibacterials to overcome the threat. As part of our program to study antimicrobial agents from plants, we investigated an ethanol (EtOH) extract of roots of P. schottii, which showed weak antibacterial activity against MRSA and VRE. Bioactivity guided fractionation of the EtOH extract afforded a new isoflavone together with four known ones, including fremontone. Combination studies of fremontone with methicillin (MIC 25 µg/mL) and vancomycin (MIC 0.5 µg/mL), exhibited a strong in-vitro MRSA activity with MIC values 6.25 µg/mL for methicilin and 0.25 µg/mL for vancomycin, indicating a 4 and 2-fold reduction in MIC respectively. It displayed a potent synergistic effect with methicillin and additive effect with vancomycin displaying a potentiation effect with both antibiotics. The antibiotic activity potentiation by prenylated flavonoids has been reported, and our study further substantiates that prenylated isoflavone fremontone, combination therapy may have a potential to reduce antibiotic-induce resistance associated with MRSA. However, further studies are needed to understand their exact role to the antibacterial effect.

Technical Abstract: Bioactivity guided fractionation of an ethanol extract of the root of Psoromanthus schotti (Family Fabaceae) afforded a new prenylated isoflavone, named schottiin (5,7,5’-trihydroxy-4’-O-methyl-6’-(3,3-dimethylallyl)-isoflavone), (1), together with four known isoflavones including fremontone (2), 5,7,4',5'-tetrahydroxy-2'-(3,3-dimethylallyl)-isoflavone (3), glycyrrhisoflavone (4) and fremontin (5), of which 3 and 4 isolated as isomeric mixture. Structures of 1-5 were determined by full spectroscopic analyses. A comprehensive 2D NMR spectral data have allowed revising the structure of fremontone as 2 from previously assigned 2A. Compound 2 showed weak in-vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) (IC50 16.1 and 19.0 µg/mL, respectively). A combination study using an in-vitro checkerboard method was carried out for fremontone (2) and methicillin, which exhibited a synergistic activity (FIC 0.4), and 2 also showed additive effect with vancomycin (FIC 1.0) against MRSA. In addition, compounds 1 and 2 showed moderate antiplasmodial activity against chloroquine-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum (IC50 3.7, 3.5, and 1.2, 1.3 µg/mL, respectively), with no cytotoxicity to mammalian Vero cells