title: Synthesis and Antimicrobial Activity of the Hybrid Molecules between Sulfonamides and Active Antimicrobial Pleuromutilin Derivative.
abstract: A series of novel hybrid molecules between sulfonamides and active antimicrobial 14-o-(3-carboxy-phenylsulfide)-mutilin were synthesized, and their in vitro antibacterial activities were evaluated by the broth microdilution. Results indicated that these compounds displayed potent antimicrobial activities in vitro against various drug-susceptible and drug-resistant Gram-positive bacteria such as Staphylococci and streptococci, including methicillin-resistant Staphylococcus aureus, and mycoplasma. In particular, sulfapyridine analog (6c) exhibited more potent inhibitory activity against Gram-positive bacteria and mycoplasma, including Staphylococcus aureus (MIC = 0.016-0.063 μg/mL), methicillin-resistant Staphylococcus aureus (MIC = 0.016 μg/mL), Streptococcus pneumoniae (MIC = 0.032-0.063 μg/mL), Mycoplasma gallisepticum (MIC = 0.004 μg/mL), with respect to other synthesized compounds and reference drugs sulfonamide (MIC = 8-128 μg/mL) and valnemulin (MIC = 0.004-0.5 μg/mL). Furthermore, comparison between MIC values of pleuromutilin-sulfonamide hybrids 6a-f with pleuromutilin parent compound 3 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.
authors.affiliation: Guangdong Dahuanong Animal Health Products Co. Ltd., Yunfu, 527400, China.|Department of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Dexue
authors.initials: D
authors.lastname: Yang
authors.affiliation: Guangdong Dahuanong Animal Health Products Co. Ltd., Yunfu, 527400, China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Lai
authors.affiliation: Department of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Guangdong Dahuanong Animal Health Products Co. Ltd., Yunfu, 527400, China.|Department of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Binghu
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Shuning
authors.initials: S
authors.lastname: Shi
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests / Q000379:methods; D009161:Mycobacterium / Q000187:drug effects; D011083:Polycyclic Compounds; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000097567:Pleuromutilins
chemical_list: D000890:Anti-Infective Agents; D004224:Diterpenes; D011083:Polycyclic Compounds; D013449:Sulfonamides; D000097567:Pleuromutilins
keywords: antibacterial activity; hybrid molecules; pleuromutilin derivative; sulfonamides