Synthesis and Antimicrobial Activity of the Hybrid Molecules between Sulfonamides and Active Antimicrobial Pleuromutilin Derivative. (18th December 2014)

• Record Type: Journal Article
• Authors: Chen, Liangzhu; Yang, Dexue; Pan, Zhikun; Lai, Lihong; Liu, Jianhua; Fang, Binghu; Shi, Shuning
• Is Part Of: Chemical biology & drug design. Volume 86:Number 2(2015:Aug.)
• Page Start: 239
• Page End: 245
• Publication Date: 2014-12-18
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12486
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12486-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A series of novel hybrid molecules between sulfonamides and active antimicrobial 14‐o‐(3‐carboxy‐phenylsulfide)‐mutilin were synthesized, and their <italic>in vitro</italic> antibacterial activities were evaluated by the broth microdilution. Results indicated that these compounds displayed potent antimicrobial activities <italic>in vitro</italic> against various drug‐susceptible and drug‐resistant Gram‐positive bacteria such as <italic>Staphylococci</italic> and <italic>streptococci</italic>, including methicillin‐resistant <italic>Staphylococcus aureus</italic>, and mycoplasma. In particular, sulfapyridine analog (<bold>6c</bold>) exhibited more potent inhibitory activity against Gram‐positive bacteria and mycoplasma, including <italic>Staphylococcus aureus</italic> (MIC = 0.016–0.063 <italic>μ</italic>g/mL), methicillin‐resistant <italic>Staphylococcus aureus</italic> (MIC = 0.016 <italic>μ</italic>g/mL), <italic>Streptococcus pneumoniae</italic> (MIC = 0.032–0.063 <italic>μ</italic>g/mL), <italic>Mycoplasma gallisepticum</italic> (MIC = 0.004 <italic>μ</italic>g/mL), with respect to other synthesized compounds and reference drugs sulfonamide (MIC = 8–128 <italic>μ</italic>g/mL) and valnemulin (MIC = 0.004–0.5 <italic>μ</italic>g/mL). Furthermore, comparison between MIC values of pleuromutilin‐sulfonamide hybrids <bold>6a–f</bold> with pleuromutilin parent compound <bold>3</bold> revealed that these modifications at 14 position side chain of the pleuromutilin with benzene sulfonamide could greatly improve the antibacterial activity especially against Gram‐positives.</p> </abstract>