Synthesis and evaluation of novel pleuromutilin derivatives with a substituted pyrimidine moiety

Yi, Yunpeng; Yang, Guan‐Zhou; Zhang, Chao; Chen, Jiongran; Liang, Jianping; Shang, Ruofeng

doi:10.1016/j.ejmech.2015.06.034

Cited by 19 publications

(7 citation statements)

References 19 publications

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“…Ling [12] and the present authors proposed that heterocyclic rings bearing polar groups at the C14 side chain of pleuromutilin derivatives improved their antibacterial activity [13,14,15]. Two classes of pleuromutilin derivatives with 1,3,4-thiadiazole and pyrimidine ring were reported and selected as a few compounds with excellent in vitro antibacterial activity against both sensitive and resistant Gram-positive bacterial strains.…”

Section: Introductionmentioning

confidence: 99%

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

Xin

et al. 2016

Molecules

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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 Escherichia coli (E. coli) and five Gram (+) inoculums. 14-O-((5-amino-benzimidazole-2-yl) thioacetyl) mutilin (3) was the most active compound and showed highest antibacterial activities. Furthermore, we evaluated the inhibition activities of compound 3 on short-term S. aureus and MRSA growth and cytochrome P450 (CYP). The bioassay results indicate that compound 3 could be considered potential antibacterial agents but with intermediate inhibition of CYP3A4.

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Section: Introductionmentioning

confidence: 99%

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

Xin

et al. 2016

Molecules

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“…The minimal inhibitory concentrations (MICs) of all active compounds 8a – i were determined by micro broth dilution method using 96 well plates, according to the method described [ 30 ]. Linezolid, ciprofloxacin and fluconazole have been used as standards; DMSO has been employed as solvent control.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Pyrimidine-oxazolidin-2-arylimino Hybrid Molecules as Antibacterial Agents

et al. 2018

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Pyrimidine-1,3-oxazolidin-2-arylimino hybrids have been synthesized as a new class of antibacterial agents. The synthetic approach exploits a Cu(II)-catalyzed intramolecular halkoxyhalogenation of alkynyl ureas, followed by a Suzuki coupling reaction with 2,4-dimethoxypyrimidin-5-boronic acid. Biological screenings revealed that most of the compounds showed moderate to good activity against two Gram-positive (B. subtilis, S. aureus) and three Gram-negative (P. aeruginosa, S. typhi, K. pneumonia) pathogenic strains. A molecular docking study, performed in the crystal structure of 50S ribosomal unit of Haloarcula marismortui, indicated that pyrimidine-oxazolidin-2-arylimino hybrids 8c and 8h exhibited a high binding affinity (−9.65 and −10.74 kcal/mol), which was in agreement with their good antibacterial activity. The obtained results suggest that the combination of pyrimidine and oxazolidone moieties can be considered as a valid basis to develop new further modifications towards more efficacious antibacterial compounds.

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“…Then it was found to block protein synthesis by inhibiting ribosomal peptidyl transferase center (PTC) through hydrophobic interaction and hydrogen bonds. Further, Yi et al [17] designed and synthesized a series of pleuromutilin derivatives possessing 6-hydroxypyrimidine moiety by semi-synthesis process, and their antibacterial activity against MRSA, methicillinresistant Staphylococcus Epidermidis (MRSE), B. subtilis and E. coli was also tested by the agar dilution method. The results indicated that compounds 14 and 15 ( Figure 4) exhibited excellent antibacterial activity against MRSA and MRSE with the MIC values of 0.125-0.25 μg mL À 1 , which was better than standard control tiamulin fumarate.…”

Section: Monopyrimidine Trisubstituted Derivativesmentioning

confidence: 99%

Recent Development of Pyrimidine‐Containing Antimicrobial Agents

Zhuang

2020

ChemMedChem

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Multidrug-resistant bacterial infections have become an important cause of clinical death in the twenty-first century. Much effort has been made to overcome this challenge. The discovery of novel antimicrobial compounds, as well as the rational use of antibacterial drugs with different structure types and mechanisms, is helping to deal with bacterial resistance. Currently, pyrimidine-containing agents are the major areas of new antibacterial drug discovery. Given their good activities and diverse mechanisms of action, many pyrimidine-containing heterocyclic compounds have become the focus of interest for many scientists. In addition, pyrimidine structure is an important part of many endogenous substances, which is an advantage that allows pyrimidine derivatives to interact with genetic materials, enzymes and other biopolymeric substances in the cell. Scientists have focused on the discovery and structural optimization of pyrimidine derivatives, which has resulted in the discovery of many novel pyrimidine derivatives with intriguing profiles. Herein we summarize the therapeutic potentials of pyrimidine compounds that are promising for antimicrobial applications over the last decade. In particular, the relationships between the structures of modified pyrimidines and their antimicrobial activity are systematically discussed.

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Synthesis and evaluation of novel pleuromutilin derivatives with a substituted pyrimidine moiety

Cited by 19 publications

References 19 publications

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

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

Synthesis and Biological Evaluation of Pyrimidine-oxazolidin-2-arylimino Hybrid Molecules as Antibacterial Agents

Recent Development of Pyrimidine‐Containing Antimicrobial Agents

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