Synthesis and Pharmacological Evaluation of Novel Pleuromutilin Derivatives with Substituted Benzimidazole Moieties

A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2016-11, Vol.21 (11), p.1488-1488
Main Authors: Ai, Xin, Pu, Xiuying, Yi, Yunpeng, Liu, Yu, Xu, Shuijin, Liang, Jianping, Shang, Ruofeng
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
antibacterial activity
Benzimidazoles - chemical synthesis
Benzimidazoles - chemistry
Benzimidazoles - pharmacology
CYP3A4
Cytochrome P-450 Enzyme Inhibitors - chemical synthesis
Cytochrome P-450 Enzyme Inhibitors - chemistry
Cytochrome P-450 Enzyme Inhibitors - pharmacology
Cytochrome P-450 Enzyme System - metabolism
Diterpenes - chemistry
Drug resistance
Escherichia coli
Escherichia coli - drug effects
Hydrogen bonds
inhibition
Methicillin-Resistant Staphylococcus aureus - drug effects
Microbial Sensitivity Tests - methods
Molecular Docking Simulation
Molecular Structure
Pharmaceuticals
pleuromutilin derivatives
Pleuromutilins
Polycyclic Compounds
Staphylococcus aureus - drug effects
Staphylococcus infections
Structure-Activity Relationship
synthesis
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Summary:A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives was evaluated in vitro for their antibacterial activity against ( ) and five Gram (+) inoculums. 14- -((5-amino-benzimidazole-2-yl) thioacetyl) mutilin ( ) was the most active compound and showed highest antibacterial activities. Furthermore, we evaluated the inhibition activities of compound on short-term and MRSA growth and cytochrome P450 (CYP). The bioassay results indicate that compound could be considered potential antibacterial agents but with intermediate inhibition of CYP3A4.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules21111488