31716-01-5Relevant articles and documents
Synthesis and antibacterial activities of novel pleuromutilin derivatives bearing an aminothiophenol moiety
Zhang, Zhao-Sheng,Huang, Yun-Zhen,Luo, Jian,Jin, Zhen,Liu, Ya-Hong,Tang, You-Zhi
, p. 1627 - 1637 (2018)
We synthesized a series of novel thioether pleuromutilin derivatives incorporating 2-aminothiophenol moieties into the C14 side chain via acylation reactions under mild conditions. We evaluated the in-vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300), Staphylococcus aureus (ATCC 29213) and Escherichia coli (ATCC 25922). The majority of the synthesized derivatives possessed moderate antibacterial activities. Compound 8 was found to be the most active antibacterial derivative against MRSA. We conducted docking experiments to understand the possible mode of interactions between compounds 8, 9b, 11a and 50S ribosomal subunit. The docking results proved that there is a reasonable correlation between the binding free energy and the antibacterial activity. Compound 8 was evaluated for its in-vivo antibacterial activity and showed higher efficacy than tiamulin against MRSA in mouse infection model.
Synthesis and biological evaluation of novel thioether pleuromutilin derivatives
Mu, Shuhua,Liu, Huixian,Zhang, Lifang,Wang, Xiaoyang,Xue, Feiqun,Zhang, Yue
, p. 1165 - 1173 (2017)
To develop new pleuromutilin derivatives as veterinary antibiotic medicines, we designed and synthesized a series of new thioether pleuromutilin derivatives possessing acylthiazolyl moiety based on previously designed derivatives. The antibacterial properties of the prepared pleuromutilin derivatives were assessed in vitro by the broth dilution method against five kinds of bacteria and the mycoplasma Mycoplasma gallisepticum (MG). All of the tested compounds displayed moderate to good antibacterial activity to meth-icillin-sensitive Staphylococcus aureus (MSSA), methicillin-sensitive Staphylococcus epidermidis (MSSE), methicillin-resistant S. aureus (MRSA), Streptococcus agalactiae (S. aga) and MG. However, the activity to Pyogeniccoccus (Pyogens) was generally poor. Compounds 13i and l showed potent antibacterial activity against MSSE and MRSA which are better than that of valnemulin. The structural modification for pleuromutilin affected the antibacterial activity. Amino substituents in the benzene ring can effectively improve activity. Compared with the analogue 13a that possesses unsubstitution benzoyl group, the nitro, methoxy, hydroxy and dichloro substituent contributed little to antibacterial activity. Increasing a methylene between benzene moiety and carbonyl group decreased the bioactivity of derivative. The analogues that obtained by the reaction of amino acids and intermediate 9 showed moderate activity.
Design, synthesis and antibacterial evaluation of novel pleuromutilin derivatives possessing piperazine linker
Gao, Mei-Ling,Zeng, Jie,Fang, Xi,Luo, Jian,Jin, Zhen,Liu, Ya-Hong,Tang, You-Zhi
, p. 286 - 295 (2017)
A series of pleuromutilin derivatives bearing piperazine ring have been reported. The in vitro antibacterial activities of the synthetic derivatives against MRSA (ATCC 43300), Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212), Enterococcus faecium (ATCC35667) and Escherichia coli (ATCC25922) were evaluated by the broth dilution method. Most of the synthesized derivatives displayed potent activities. Compounds 11c, 12a and 12c were found to be the most active antibacterial derivatives against MRSA (minimum inhibitory concentration = 0.015 μg/mL). The binding of compounds 11c, 12a and 12c to the 50s ribosome were investigated by molecular modeling. Compound 11c possessed lower binding free energy compared with compounds 12a and 12c. Compound 11c was further evaluated in MRSA systemic infection model and displayed superior in vivo efficacy to that of tiamulin.
Design, synthesis, and antibacterial activity of novel pleuromutilin derivatives bearing an amino thiazolyl ring
Ling, Yong,Wang, Xinyang,Wang, Hui,Yu, Jianghe,Tang, Junming,Wang, Donggeng,Chen, Guangtong,Huang, Jinhua,Li, Yuqin,Zheng, Heng
, p. 638 - 646 (2012)
A series of novel pleuromutilin derivatives containing the amino thiazolyl ring were designed, synthesized, and evaluated for their antibacterial activities in vitro against Gram-positive clinical bacteria. All the target compounds showed better aqueous s
Synthesis and pharmacological evaluation of novel pleuromutilin derivatives with substituted benzimidazole moieties
Ai, Xin,Pu, Xiuying,Yi, Yunpeng,Liu, Yu,Xu, Shuijin,Liang, Jianping,Shang, Ruofeng
, (2016)
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 b
Design, synthesis and biological evaluation of novel pleuromutilin derivatives as potent anti-MRSA agents targeting the 50S ribosome
Huang, Si-Yu,Wang, Xiao,Shen, Ding-Yi,Chen, Fang,Zhang, Guang-Yu,Zhang, Zhe,Li, Kang,Jin, Zhen,Du, Dan,Tang, You-Zhi
, (2021)
A series of novel pleuromutilin derivatives were designed and synthesized with 1,2,4-triazole as the linker connected to benzoyl chloride analogues under mild conditions. The in vitro antibacterial activities of the synthesized derivatives against four st
Design, synthesis and antibacterial activity evaluation of pleuromutilin derivatives according to twin drug theory
Cui, Ge,Liu, Hui-Xian,Ma, Dong-Lai,Xue, Fei-Qun,Zhang, Yue
, (2021)
A series of novel pleuromutilin derivatives were designed and synthesized based on the twin drugs theory. Piperazinyl and thioether were used as the linkage to connect the pleuromutilin nuclear and sulfonamide to improve the biological activity and water
Design, synthesis, and structure–activity relationship studies of novel pleuromutilin derivatives having a piperazine ring
Luo, Jian,Yang, Qiu-E,Yang, Yuan-Yuan,Tang, You-Zhi,Liu, Ya-Hong
, p. 699 - 709 (2016)
A series of novel pleuromutilin derivatives possessing piperazine moieties were synthesized under mild conditions. The in vitro antibacterial activities of these derivatives against Staphylococcus aureus and Escherichia coli were tested by the agar dilution method. Structure–activity relationship studies resulted in compounds 11b, 13b, and 14a with the most potent in vitro antibacterial activity among the series (minimal inhibitory concentration?=?0.0625–0.125?μg/mL). The binding of compounds 11b, 13b, and 14a to the E.?coli ribosome was investigated by molecular modeling, and it was found that there is a reasonable correlation between the binding free energy and the antibacterial activity.
Synthesis and antibacterial activities of novel pleuromutilin derivatives
Yi, Yunpeng,Fu, Yunxing,Wang, Keli,Shui, Yongzhen,Cai, Jing,Jia, Zhong,Niu, Biao,Liang, Jianping,Shang, Ruofeng
, (2018)
Pleuromutilin derivatives 4a–h, 5a–g, and 6a–d were synthesized and characterized by IR, 1H NMR, and 13C NMR. All synthetic compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus (ATCC 25923),
Design, synthesis and biological evaluation of pleuromutilin-Schiff base hybrids as potent anti-MRSA agents in vitro and in vivo
Li, Bo,Zhang, Zhe,Zhang, Jian-Feng,Liu, Jie,Zuo, Xiang-Yi,Chen, Fang,Zhang, Guang-Yu,Fang, Han-Qing,Jin, Zhen,Tang, You-Zhi
, (2021/06/22)
A series of pleuromutilin derivatives with 1,2,4-triazole-3-substituted Schiff base structure were designed and synthesized under mild conditions. The in vitro antibacterial activities of the synthesized derivatives against 4 strains of Staphylococcus aureus (MRSA ATCC 43300, S.aureus ATCC 29213, S.aureus 144 and S.aureus AD3) and 1 strain of E. coli (ATCC 25922) were evaluated by the broth dilution method. Among these derivatives, compound 60 exhibited superior in vitro antibacterial effect against MRSA (MIC = 0.25 μg/mL) than tiamulin (MIC = 0.5 μg/mL), and compound 60 (?2.28 log10 CFU/mL) also displayed superior in vivo antibacterial efficacy than tiamulin (?1.40 log10 CFU/mL) in reducing MRSA load in the mouse thigh infection model. The time-kill study and the post-antibiotic effect study indicated that compound 60 showed a faster bactericidal kinetic and longer PAE time (exposure to 2 × MIC and 4 × MIC for 2 h, the PAE was 4.06 and 4.27 h) against MRSA compared with tiamulin (exposure to 2 × MIC and 4 × MIC for 2 h, the PAE was 1.72 and 2.14 h). Meanwhile, most of these compounds had no significant inhibitory effect on RAW 264.7 cells and HepG2 cells at the concentration of 4 μg/mL. Additionally, the development of resistance study showed that MRSA did not easily develop resistance against compound 60 compared with tiamulin after induction for 8 passages.
Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
-
Paragraph 0056; 0070; 0090-0091, (2021/07/24)
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
