Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3',7-Dimethyl ether.

Shaymaa Al-Majmaie,M Mukhlesur Rahman,Anupam Das Talukdar,Satyajit D Sarker,Lutfun Nahar,Priyanka Saha,Sushmita Nath,George P Sharples

doi:10.3390/molecules26041114

Abstract

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans. Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin (9), chalepensin (10), rutamarin (11), rutin 3′-methyl ether (14), rutin 7,4′-dimethyl ether (15), 6-hydroxy-rutin 3′,7-dimethyl ether (16) and arborinine (18) were in the range of 32–128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis, and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 μg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

Highlights

Antibiotic resistance is a global public health problem and is most common in developing countries [1]
We report on the isolation, identification, anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of several compounds from R. chalepensis, collected in Iraq, against a panel of MRSA strains including, ATCC25923, SA1199B, XU212, MRSA-274819 and EMRSA15, and in silico studies on the two most active anti-MRSA compounds from this plant, chalepensin (10) and 6-hydroxy-rutin 3,7-dimethyl ether (16)
Following the initial antimicrobial screening of the crude extracts of R. chalepensis, the minimum inhibitory concentration (MIC) of 6.25 × 10−1 mg/mL was chosen as the minimum threshold of activity for any extract for further analysis, leading to the isolation of compounds responsible for their antimicrobial activity

Summary

Introduction

Antibiotic resistance is a global public health problem and is most common in developing countries [1]. Microorganisms, bacteria, develop resistance to antimicrobial drugs, mainly because of clinical, cellular and molecular factors. The unlicensed medicine suppliers, uncontrolled antibiotic sales, and availability of over-the-counter antibiotics without a prescription in developing countries, have led to an exponential increase in drug resistance [4]. This dire situation of antimicrobial drug resistance has prompted the search for novel compounds, those from natural sources, with potential antimicrobial properties against various drug-resistant microbial strains

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