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

Molecules

KhalidZ. Alshali¹  HossamM. Abdallah²  MahmoudA. Elfaky²  AbdulrahmanE. Koshak²  MaanT. Khayat³  MoustafaE. El-Araby³  AliM. El-Halawany⁴ 

[1] Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt;

关键词: β-lactamase;    Clutia myricoides;    Klebsiella pneumoniae;    antimicrobial resistance;    bio-guided fractionation;    molecular docking;   

DOI  :  10.3390/molecules25112566

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown