Abstract
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 Clutia myricoides (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 (2) and Saudin-I (5) in addition to three known compounds that were identified as chrysophanol (1), stigmasterol (3) and β-sitosterol (4). Antibacterial and anti ESBL activities of the isolated compounds were performed. No antibacterial activities were detected for any of the tested compounds. Meanwhile, compound 2 showed promising anti ESBL activity. Compound 2 has shown an obvious activity against K. pneumoniae 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 2, molecular docking was carried out against CTX-M-27 ESBL. The results showed binding site interactions strikingly different from its analogue, compound 1, allowing compound 2 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.
Highlights
Contagious diseases are the second significant reason for death around the world
Management of Acinetobacter baumannii and Pseudomonas aeruginosa, which are connected to severe infections, is greatly troublesome as a result of their resistance to antimicrobials by various mechanisms [1]
Klebsiella pneumoniae is a serious microbe related with numerous hospitals acquired infections while the level of β-lactamase producing Escherichia coli began to wind up progressively harder to manage
Summary
Contagious diseases are the second significant reason for death around the world. The capacity to resist various classes of antimicrobial agents is a key factor that enables the survival of pathogens in Molecules 2020, 25, 2566; doi:10.3390/molecules25112566 www.mdpi.com/journal/moleculesMolecules 2020, 25, 2566 nosocomial settings. Management of Acinetobacter baumannii and Pseudomonas aeruginosa, which are connected to severe infections, is greatly troublesome as a result of their resistance to antimicrobials by various mechanisms [1]. Klebsiella pneumoniae is a serious microbe related with numerous hospitals acquired infections while the level of β-lactamase producing Escherichia coli began to wind up progressively harder to manage. Presence of blaCTX-M, blaSHV, and the blaTEM genes among the β-lactamase producing K. pneumoniae and E. coli are accounted for around the world [2]. The β-lactamases are the principal mechanism of resistance to β-lactam antimicrobials [3]. Gram-negative microorganisms are more unaffected by antibiotics than Gram-positive ones. This is attributable to transmembrane efflux [4]
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