Bioassay Guided Isolation and Docking Studies of a Potential β-Lactamase Inhibitor from Clutia myricoides

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 11; p. 2566
• Main Authors: Elfaky, Mahmoud A, El-Halawany, Ali M, Koshak, Abdulrahman E, Alshali, Khalid Z, El-Araby, Moustafa E, Khayat, Maan T, Abdallah, Hossam M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.05.2020; MDPI
• Subjects: Amides; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; antimicrobial resistance; beta-Lactamase Inhibitors - chemistry; beta-Lactamase Inhibitors - pharmacology; beta-Lactamases - chemistry; Binding Sites; bio-guided fractionation; Biocompatibility; Biological Assay; Carbon; Cephalosporins; Cephalosporins - chemistry; Chloroform; Chloroform - chemistry; Chrysophanic acid; Clutia myricoides; E coli; Enlargement; Escherichia coli - drug effects; Escherichia coli - enzymology; Fractionation; Furans - chemistry; Hospitals; Infectious diseases; Inhibitors; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - enzymology; Magnetic Resonance Spectroscopy; Magnoliopsida - chemistry; Microbial Sensitivity Tests; Models, Molecular; Molecular docking; Molecular Docking Simulation; Nosocomial infection; Pathogens; Protein Binding; Toxicity; β-Lactam antibiotics; β-lactamase; Clutia myricoides; bio-guided fractionation; molecular docking; antimicrobial resistance; β-lactamase; Klebsiella pneumoniae
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25112566

Infectious diseases are the second major cause of death worldwide, and the ability to resist multiple classes of antibiotics is the key factor in enabling pathogenic organisms to survive and spread in the nosocomial environment. Unfortunately, the available β-lactamase inhibitors are not efficient against β-lactamase B, C, and D which necessitates discovering either broad spectrum β-lactamase inhibitors or new β-lactam antibiotics resistant to bacterial enzymes. In this regard, products of natural origin have prompted the disclosure of new compounds and medicinal leads. Chloroform fraction of (Soa'bor) showed a pronounced activity against extended-spectrum β-lactamase (ESBL) strains. Bio-guided fractionation resulted in isolation of two new compounds; 2-methoxy chrysophanol ( ) and Saudin-I ( ) in addition to three known compounds that were identified as chrysophanol ( ), stigmasterol ( ) and β-sitosterol ( ). Antibacterial and anti ESBL activities of the isolated compounds were performed. No antibacterial activities were detected for any of the tested compounds. Meanwhile, compound showed promising anti ESBL activity. Compound has shown an obvious activity against ATCC 700603 with a marked enlargement of inhibition zones (>5mm) in combination with third generation cephalosporin antibiotics. To further understand the mechanism of action of compound , molecular docking was carried out against CTX-M-27 ESBL. The results showed binding site interactions strikingly different from its analogue, compound , allowing compound to be active against ESBL. These results proposed the concomitant use of these active compounds with antibiotics that would increase their efficiency. Nevertheless, the interaction between this active compound and antibiotics should be taken into consideration. Therefore, in order to evaluate the safety of this active compound, further in vitro and in vivo toxicity assays must be carried out.