PMID- 35056143
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220128
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Jan 11
TI  - In Silico-Based Discovery of Natural Anthraquinones with Potential against 
      Multidrug-Resistant E. coli.
LID - 10.3390/ph15010086 [doi]
LID - 86
AB  - E. coli is a Gram-negative bacterium that causes different human infections. 
      Additionally, it resists common antibiotics due to its outer protective membrane. 
      Natural products have been proven to be efficient antibiotics. However, plant 
      natural products are far less explored in this regard. Accordingly, over 16,000 
      structures covering almost all African medicinal plants in AfroDb in a 
      structural-based virtual screening were used to find efficient anti-E. coli 
      candidates. These drug-like structures were docked into the active sites of two 
      important molecular targets (i.e., E. coli's Ddl-B and Gyr-B). The top-scoring 
      hits (i.e., got docking scores < -10 kcal/mol) produced in the initial virtual 
      screening (0.15% of the database structures for Ddl-B and 0.17% of the database 
      structures for Gyr-B in the database) were further refined using molecular 
      dynamic simulation-based binding free energy (DeltaG) calculation. Anthraquinones 
      were found to prevail among the retrieved hits. Accordingly, readily available 
      anthraquinone derivatives (10 hits) were selected, prepared, and tested in vitro 
      against Ddl-B, Gyr-B, multidrug-resistant (MDR) E. coli, MRSA, and VRSA. A number 
      of the tested derivatives demonstrated strong micromolar enzyme inhibition and 
      antibacterial activity against E. coli, MRSA, and VRSA, with MIC values ranging 
      from 2 to 64 microg/mL. Moreover, both E. coli's Ddl-B and Gyr-B were inhibited by 
      emodin and chrysophanol with IC(50) values comparable to the reference inhibitors 
      (IC(50) = 216 +/- 5.6, 236 +/- 8.9 and 0.81 +/- 0.3, 1.5 +/- 0.5 microM for Ddl-B and Gyr-B, 
      respectively). All of the active antibacterial anthraquinone hits showed low to 
      moderate cellular cytotoxicity (CC(50) > 50 microM) against human normal fibroblasts 
      (WI-38). Furthermore, molecular dynamic simulation (MDS) experiments were carried 
      out to reveal the binding modes of these inhibitors inside the active site of 
      each enzyme. The findings presented in this study are regarded as a significant 
      step toward developing novel antibacterial agents against MDR strains.
FAU - Alhadrami, Hani A
AU  - Alhadrami HA
AUID- ORCID: 0000-0002-4822-1895
AD  - Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, 
      King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia.
AD  - Molecular Diagnostic Lab, King Abdulaziz University Hospital, King Abdulaziz 
      University, P.O. Box 80402, Jeddah 21589, Saudi Arabia.
AD  - Special Infectious Agent Unit, King Fahd Medical Research Center, King Abdulaziz 
      University, P.O. Box 80402, Jeddah 21589, Saudi Arabia.
FAU - Abdulaal, Wesam H
AU  - Abdulaal WH
AUID- ORCID: 0000-0002-2510-1946
AD  - Cancer and Mutagenesis Unit, Department of Biochemistry, Faculty of Science, King 
      Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80402, Jeddah 
      21589, Saudi Arabia.
FAU - Hassan, Hossam M
AU  - Hassan HM
AUID- ORCID: 0000-0003-0174-4434
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 
      62513, Egypt.
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 
      62511, Egypt.
FAU - Alhakamy, Nabil A
AU  - Alhakamy NA
AUID- ORCID: 0000-0002-3826-1519
AD  - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, P.O. 
      Box 80402, Jeddah 21589, Saudi Arabia.
FAU - Sayed, Ahmed M
AU  - Sayed AM
AUID- ORCID: 0000-0002-1442-183X
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 
      62513, Egypt.
LA  - eng
GR  - IFPHI-214-130-2020/Ministry of Education and King Abdulaziz University/
PT  - Journal Article
DEP - 20220111
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC8778091
OTO - NOTNLM
OT  - AfroDb
OT  - Ddl-B
OT  - E. coli
OT  - Gyr-B
OT  - anthraquinone
OT  - virtual screening
COIS- The authors declare no conflict of interest.
EDAT- 2022/01/22 06:00
MHDA- 2022/01/22 06:01
PMCR- 2022/01/11
CRDT- 2022/01/21 01:13
PHST- 2021/12/20 00:00 [received]
PHST- 2022/01/07 00:00 [revised]
PHST- 2022/01/09 00:00 [accepted]
PHST- 2022/01/21 01:13 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/01/22 06:01 [medline]
PHST- 2022/01/11 00:00 [pmc-release]
AID - ph15010086 [pii]
AID - pharmaceuticals-15-00086 [pii]
AID - 10.3390/ph15010086 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2022 Jan 11;15(1):86. doi: 10.3390/ph15010086.