Presenter: Mallika Kumarihamyhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1001/thumbnail.jp

Khan, Shabana

Kumarihamy, Mallika

Muhammad, Ilias

Tripathi, Siddharth K.

English

eGrove (Univ. of Mississippi)

University of Mississippi eGrove Annual Poster Session 2021 Annual Poster Session 10-19-2021 Schottiin, a New Prenylated Isoflavone from Psorothamnus schottii and Antibacterial Synergism Studies between Methicillin and Fremontone against MRSA Mallika Kumarihamy University of Mississippi, mkumarih@olemiss.edu Siddharth K. Tripathi University of Mississippi Shabana Khan University of Mississippi Ilias Muhammad University of Mississippi Follow this and additional works at: https://egrove.olemiss.edu/pharm_annual_posters_2021  Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Kumarihamy, Mallika; Tripathi, Siddharth K.; Khan, Shabana; and Muhammad, Ilias, "Schottiin, a New Prenylated Isoflavone from Psorothamnus schottii and Antibacterial Synergism Studies between Methicillin and Fremontone against MRSA" (2021). Annual Poster Session 2021. 2. https://egrove.olemiss.edu/pharm_annual_posters_2021/2 This Book is brought to you for free and open access by the Annual Poster Session at eGrove. It has been accepted for inclusion in Annual Poster Session 2021 by an authorized administrator of eGrove. For more information, please contact egrove@olemiss.edu. ABSTRACTMETHODSDISCUSSION & CONCLUSIONS REFERENCE & ACKNOWLEDGMENTBioactivity guided isolation of an ethanol extract of the root of Psoromanthus schottii (Family Fabaceae) affordeda new prenylated isoflavone, named schottiin (1), together with four other isoflavones, including fremontone (2),5,7,4´,5´-tetrahydroxy-2´-(3,3-dimethylallyl)-isoflavone (3), glycyrrhisoflavone (4) and fremontin (5), of which 3and 4 identified as isomeric mixture. Structures of 1-5 were determined by full spectroscopic analyses. Acomprehensive 2D NMR spectral data has allowed revising the structure of fremontone as 2 from previouslyreported 2A. Compound 2 showed weak in-vitro antibacterial activity against methicillin-resistant Staphylococcusaureus (MRSA). A combination study using a checkerboard assay between fremontone (2) and methicillinexhibited a synergistic activity with 8-fold decrease in MIC of methicillin, as well as an additive effect withvancomycin against MRSA ATCC 1708. Compounds 1 and 2 also showed moderate antiplasmodial activityagainst chloroquine-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum with no cytotoxicity tomammalian Vero cells.Schottiin, a New Prenylated Isoflavone from Psorothamnus schottii and Antibacterial Synergism Studies between Methicillin and Fremontone against MRSA Mallika Kumarihamy1, Siddharth K. Tripathi1, Shabana Khan1,2, and Ilias Muhammad11National Center for Natural Products Research, 2Department of Biomolecular Sciences, Research Institute for Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.Kumarihamy et al. (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, DOI: 10.1080/14786419.2021.1937157.This work is supported by USDA-ARS SCA # 58-6060-6-015. We thank Drs. Vijayakumar Raman, Mei Wang, Bharathi Avula, Mr. John Trott and Ms. Maria Bennett of NCNPR, University of Mississippi, for providing information on plant, acquiring ESI-MS, HRMS, and technical assistance in antiplasmodial and antimicrobial testings, respectively. A comprehensive 2D NMR spectral data has allowed revising the structure of fremontone as 2 from previously reported 2A (Table 1 &Figures 1, 2). Among them, schottiin (1) showed weak antifungal activity (IC50 19 µg/mL) against C. neoformans. Compound 2, whichcontains both 1,1-dimethyl and 3.3-dimethylallyl prenylation groups in the ring B showed weak in-vitro antibacterial activity againstMRSA, but a combination study, using a checkerboard method, of 2 and methicillin exhibited an 8-fold more potent activity (i.e., MIC12.5 µg/mL), compared to methicillin (MIC 100 µg/mL), while vancomycin and 2 was found to be 2-fold more active (MIC 0.25 µg/mL)than vancomycin alone (MIC 0.5 µg/mL). On the other hand, the MIC value of 2 was reduced from 12.5 to 3.12 µg/mL, a 4-fold reductiondue to synergism with methicillin, thus 2 displayed a potent synergistic effect (FIC = 0.375) with methicillin and an additive effect withvancomycin (FIC = 1.0) displaying a potentiation effect with both antibiotics (Table 2).The antimicrobial activity of prenylated flavonoids and their potentiation effect with antibiotics against MRSA have been reported. Ourstudy further substantiates that prenylated isoflavone (2) adjuvant therapy with methicillin, may have a potential value to addressantibiotic-induce resistance by MRSA. However, further studies are needed to understand their exact role to combat antibacterialresistance. Compounds 1 and 2 also showed moderate anti-plasmodial activity against CQ-sensitive (D6) and -resistant (W2) strains ofP. falciparum (IC50 3.7, 3.5, and 1.2, 1.3 µg/mL, respectively, vs. IC50 of reference standards chloroquine and artemisinin 0.02, 0.16, and0.005, 0.003 µg/mL, respectively), with no cytotoxicity to mammalian Vero cells (IC50 > 4.76 µg/mL).Table 1. 1H and 13C NMR Spectroscopic data  for compounds 1-2Table 2. Combination study of compound 2 by checkerboard assay against MRSAa) MIC of 2 reduced from 12.5 to 3.12 μg/mL, b) MIC of methicillin reduced from >50 to 12.5 μg/mL, c) MIC of vancomycin reduced from 0.5 to 0.25 μg/mL, d) MIC of 2 reduced from 12.5 to 6.25 μg/mL. . In general, when the MIC of each compound-decreased 4X in the presence of the other, it is considered synergistic; reduction of MIC in parentheses. Antimicrobial assays were carried out in triplicate.Figure 2: COSY  and  key HMBC  correlations of  1 and  2 Figure 1. Structures of compounds isolated from P. schottiiRoot of P. schottiSouthwest Desert FloraAntimicrobial Assay Antimicrobial assays were carried out using a modified version of the CLSI (formerly NCCLS) method. Antimicrobial Combination Study by Checkerboard Method The combination study of the compounds was carried out inMRSA using a standard Checkerboard method. Thefractional inhibitory concentration (FIC) was calculated byusing the following formula: FIC = [A*]/[A] + [B*]/[B], where[A*] is MIC of compound A in the presence of compound B,[A] is MIC of compound A alone, [B*] is MIC of compound Bin the presence of compound A, and [B] is MIC of compoundB alone. FIC: ≤0.5 = synergistic; 0.51-1.0 = additive; 1.1-2.0= indifferent; >2.0 = antagonisticAntiplasmodial and Cytotoxicity AssayThe antiplasmodial assay was performed against D6(chloroquine sensitive) and W2 (chloroquine resistant) strainsof P. falciparum using the in-vitro assay. The cytotoxicity oftest samples was determined against a mammalian cell line(VERO) in order to calculate the selectivity index ofantimalarial activity.aRecorded at 100 mHz, bRecorded at 400 MHz. cCoupling constant (J) values in Hz. *in CDCl3/methanol-d4.**in DMSO-d6

Schottiin, a New Prenylated Isoflavone from Psorothamnus schottii and Antibacterial Synergism Studies between Methicillin and Fremontone against MRSA

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Schottiin, a New Prenylated Isoflavone from Psorothamnus schottii and Antibacterial Synergism Studies between Methicillin and Fremontone against MRSA

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