PMID- 33422909
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20210831
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 31
DP  - 2021 Feb 1
TI  - Nosiheptide analogues as potential antibacterial agents via dehydroalanine region 
      modifications: Semi-synthesis, antimicrobial activity and molecular docking 
      study.
PG  - 115970
LID - S0968-0896(20)30800-2 [pii]
LID - 10.1016/j.bmc.2020.115970 [doi]
AB  - The frequent and inappropriate use of antibiotics aggravate the variation and 
      evolution of multidrug-resistant bacteria, posing a serious threat to public 
      health. Nosiheptide (NOS) has excellent lethality against a variety of 
      Gram-positive bacteria, however the physical and chemical drawbacks hamper its 
      routine application in clinical practice. In this study, by using NOS as the 
      starting material, a total of 15 NOS analogues (2a-4e) were semi-synthesized via 
      its dehydroalanine residue reacting with monosubstituted anilines. In vitro 
      antimicrobial susceptibilities of NOS and its analogues against two 
      methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant 
      Enterococcus faecium (VRE) clinical isolates were determined by broth 
      microdilution assay to determine the minimum inhibitory concentration (MIC). 
      Antimicrobial susceptibility testing data shown that most of the NOS analogues 
      had a better antibacterial effect than the parent compound, with compound 3c 
      exhibiting the highest antibacterial activity against VRE (MIC = 0.0078 mg/L) and 
      MRSA (MIC < 0.0039 mg/L). Molecular docking of synthetic compounds was also 
      performed to verify the binding interactions of NOS analogues with the target. 
      Our data indicated that compound 3c possesses stronger and more complex 
      intermolecular force than other analogues, which is consistent with the results 
      of the biological activity evaluation. Overall, this study identified a number of 
      potential antibacterial NOS analogues that could act as potent therapeutic agents 
      for multidrug-resistant bacterial infections.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Fan, Yafei
AU  - Fan Y
AD  - Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, 
      School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, 
      China.
FAU - Chen, Hangfei
AU  - Chen H
AD  - Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University 
      School of Medicine, Hangzhou, 310016, China.
FAU - Mu, Ning
AU  - Mu N
AD  - Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, 
      School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, 
      China.
FAU - Wang, Wengui
AU  - Wang W
AD  - Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, 
      School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, 
      China.
FAU - Zhu, Kongkai
AU  - Zhu K
AD  - School of Biological Science and Technology, University of Jinan, Jinan 250022, 
      China; Drug Discovery and Design Center, State Key Laboratory of Drug Research, 
      Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi 
      Road, Shanghai 201203, China. Electronic address: bio_zhukk@ujn.edu.cn.
FAU - Ruan, Zhi
AU  - Ruan Z
AD  - Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University 
      School of Medicine, Hangzhou, 310016, China. Electronic address: r_z@zju.edu.cn.
FAU - Wang, Shoufeng
AU  - Wang S
AD  - Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, 
      School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, 
      China. Electronic address: chm_wangsf@ujn.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201231
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Thiazoles)
RN  - 98RA387EKY (dehydroalanine)
RN  - F7YI574GFD (nosiheptide)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine/*analogs & derivatives/chemistry/pharmacology
MH  - Anti-Bacterial Agents/chemical synthesis/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance, Multiple, Bacterial/drug effects
MH  - Enterococcus faecium/*drug effects
MH  - Methicillin-Resistant Staphylococcus aureus/*drug effects
MH  - Microbial Sensitivity Tests
MH  - *Molecular Docking Simulation
MH  - Molecular Structure
MH  - Structure-Activity Relationship
MH  - Thiazoles/chemical synthesis/chemistry/pharmacology
OTO - NOTNLM
OT  - Antimicrobial activity
OT  - Molecular docking
OT  - Nosiheptide analogues
OT  - Semi-synthesis
EDAT- 2021/01/11 06:00
MHDA- 2021/09/01 06:00
CRDT- 2021/01/10 20:37
PHST- 2020/10/29 00:00 [received]
PHST- 2020/12/15 00:00 [revised]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2021/01/11 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2021/01/10 20:37 [entrez]
AID - S0968-0896(20)30800-2 [pii]
AID - 10.1016/j.bmc.2020.115970 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2021 Feb 1;31:115970. doi: 10.1016/j.bmc.2020.115970. Epub 2020 
      Dec 31.