- Design, synthesis and biological evaluation of pleuromutilin-Schiff base hybrids as potent anti-MRSA agents in vitro and in vivo
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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.
- 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
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- Pleuromutilin derivative with 1,2,4-triazole Schiff base as well as preparation and application of pleuromutilin derivative
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The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with 1,2,4-triazole Schiff base as well as preparation and application of the pleuromutilin derivative. The pleuromutilin derivative with 1,2,4-triazole Schiff base is a compound represented by a formula 2 or a pharmaceutically acceptable salt thereof, and a solvate, an enantiomer, a diastereoisomer, a tautomer or a mixture of the solvate, the enantiomer, the diastereoisomer and the tautomer of the compound of formula 2 or the pharmaceutically acceptable salt thereof, the compoundnot only has good in-vitro antibacterial activity, but also has the advantage of low preparation cost compared with valnemulin and retapamulin, so that the compound is particularly suitable for beingused as a novel antibacterial drug for preventing and treating human or animal bacterial infectious diseases, particularly infectious diseases caused by drug-resistant staphylococcus aureus.
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Paragraph 0106-0108
(2020/10/04)
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- A containing sulfide [...] myricetin derivatives, their preparation and use
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The invention discloses a containing sulfide [...] myricetin derivatives, their preparation and use, its general structure is as follows [A] shown: wherein R is phenyl, substituted phenyl, aryl heterocyclic; n is the number of the carbon in the carbon chain are 3, 4, 5. The invention of tobacco mosaic virus, citrus ulcer bacteria and rice the dried bean curd is dry bacteria there are better control effect.
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Paragraph 0031; 0037; 0038
(2019/04/09)
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- Synthesis and antibacterial and antiviral activities of myricetin derivatives containing a 1,2,4-triazole Schiff base
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A series of novel myricetin derivatives containing a 1,2,4-triazole Schiff base were designed and synthesized. Their structures were systematically characterized using 1H NMR, 13C NMR, and HRMS. During antibacterial bioassays, 6f, 6i, and 6q demonstrated a good inhibitory effect against Xanthomonas axonopodis pv. citri (Xac), with half-maximal effective concentration (EC50) values of 10.0, 9.4, and 8.8 μg mL-1, respectively, which were better than those of bismerthiazol (54.9 μg mL-1) and thiodiazole copper (61.1 μg mL-1). Note that 6w demonstrated a good inhibitory effect against Ralstonia solanacearum (Rs) with and EC50 value of 15.5 μg mL-1, which was better than those of bismerthiazol (55.2 μg mL-1) and thiodiazole copper (127.9 μg mL-1). Similarly, 6a, 6d, and 6e demonstrated a good inhibitory effect against Xanthomonas oryzae pv. oryzae (Xoo) with EC50 values of 47.1, 61.2, and 61.0 μg mL-1, respectively, which were better than those of bismerthiazol (148.2 μg mL-1) and thiodiazole copper (175.5 μg mL-1). Furthermore, we used scanning electron microscopy (SEM) to study the possible sterilization process of the target compound 6q against Xac. The results indicated the possibility of destroying the bacterial cell membrane structure, resulting in an incomplete bacterial structure, and thus achieving inhibition. Furthermore, antiviral bioassays revealed that most compounds exhibited excellent antiviral activity against tobacco mosaic virus (TMV) at a concentration of 500 μg mL-1. The results of the molecular docking studies for 6g with TMV-CP (PDB code: 1EI7) showed that compound 6g had partially interacted with TMV-CP. Therefore, mechanistic studies of the action of compound 6g could be further studied based on that.
- Chen, Ying,Li, Pu,Su, Shijun,Chen, Mei,He, Jun,Liu, Liwei,He, Ming,Wang, Hua,Xue, Wei
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p. 23045 - 23052
(2019/08/12)
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- triazole Greece ioof alkali compound, preparation method thereof, and use thereof
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The invention relates to the field of thrombotic disease related drugs, belongs to triazole Schiff base compounds with brand new structures and derivatives of the triazole Schiff base compounds and particularly relates to PAR (Protease Activated Receptor)-1 antagonists with triazole Schiff base structures, preparation methods of the PAR-1 antagonists, pharmaceutical compositions containing the PAR-1 antagonists and applications of the PAR-1 antagonists to preparation of drugs for treating thrombotic diseases. The compounds have the structures as shown in the specification, wherein all the substituent groups are defined as the specification.
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Paragraph 0030; 0032
(2016/10/08)
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- Extractive spectrophotometric determination of ruthenium(III) with 4-(benzylideneimino)-5-methyl-4H-1,2,4-triazole-3-thiol
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A simple, highly sensitive and selective spectrophotometric method is proposed for the extraction of microgram level concentration of ruthenium(III) with 4-(benzylideneimino)-5-methyl-4H-1,2,4-triazole-3-thiol (BIMTT) as an extractant at pH 5.4 in chlorof
- Vidhate,Gadekar,Lande,Arbad
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experimental part
p. 109 - 112
(2010/06/19)
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