Design, synthesis and biological evaluation of amide-pyridine derivatives as novel dual-target (SE, CYP51) antifungal inhibitors

Sun, Bin; Dong, Yue; Lei, Kang; Wang, Jian; Zhao, Liyu; Liu, Min

doi:10.1016/j.bmc.2019.02.009

Cited by 34 publications

(20 citation statements)

References 27 publications

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“…Changes in the activity of bacterial cells under the influence of pyridine derivatives probably result from the strong activation of oxidative stress in the bacterial cell at its cell membrane, which, at a later stage, leads to apoptosis as a result of further penetration into the genetic material. This leads to its destruction through the modification and inhibition of the replication apparatus leading to apoptosis [ 50 , 51 , 52 , 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…The obtained results constitute the basis for the continuation of research into other bacterial strains associated with human civilization diseases and identification of hospital infections. In addition to the MIC and MBC tests, the analyzed pyridine derivatives were analyzed for the digestion of modified plasmids isolated from strains K12 and R2, R3 and R4 by the Fpg protein with N-glycosylase/AP lyase activity [ 50 , 51 , 52 , 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…At present, it is believed in many domestic and foreign laboratories that this protein is an extremely precise and very sensitive marker of DNA oxidative damage formed in the bacterial cell in the process of oxidative stress induced by factors of internal origin, e.g., lipid peroxidation, alkylation, methylation of DNA bases, etc., as well as external origin such as ionizing radiation. It is estimated that the amount of oxidation in bacterial DNA at the level of 3–4%, caused by the aforementioned factors and recognized by the Fpg enzyme, is an important indicator of the modification of individual DNA bases, including guanine, leading to the formation of 8oxoguanine (8oxoG), FapyGua (FapyG) or modification of adenine to form Fapy Ade (FapyA) in a particular matrix [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…All bacterial strains were received and statistically analysed, as described in [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ].…”

Section: Methodsmentioning

confidence: 99%

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Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

et al. 2021

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A preliminary study of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines as new potential antimicrobial drugs was performed. Special emphasis was placed on the selection of the structure of target pyridine derivatives with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R2–R4 (with different lengths of LPS in its structure) were used. Studied target compounds were provided with yields ranging from 53% to 91% by the lipase-catalyzed one pot multicomponent reaction of various aromatic aldehydes with malononitrile, and thiols. The presented work showed that the antibacterial activity of the studied pyridines depends on their structure and affects the LPS of bacteria. Moreover, the influence of the pyridines on bacteria possessing smooth and rough LPS and oxidative damage to plasmid DNA caused by investigated compounds was indicated. Additionally, the modification of the bacterial DNA with the tested compounds was performed to detect new potential oxidative damages, which are recognized by the Fpg protein. The obtained damage modification values of the analyzed compounds were compared with the modifications after antibiotics were used in this type of research. The presented studies demonstrate that 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines can be used as substitutes for known antibiotics. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

et al. 2021

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“…The in vitro antifungal evaluation suggested that the title compounds have broad-spectrum potential against drug-resistant fungal strains with MIC range of 0.125–2.00 µg/mL compared to the standard drug fluconazole. In addition, the ADME and toxicity assays were also performed which further demonstrated that amide-pyridine derivatives did not show genotoxicity and have drug-like properties [ 39 ] ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

Pyridine Scaffolds, Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives

et al. 2021

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Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.

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Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1‐b][1,3,4]Thiadiazole Moiety

Yang,

Jiao,

Quan

et al. 2024

Chemistry & Biodiversity

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Four series of novel pyridine derivatives (17a–i, 18a–i, 19a–e, and 20a–e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4‐F substituted compound 17d (MIC = 0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC = 1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17a and 17d are equivalent to the positive control compound fluconazole (MIC = 8 µg/mL). Furthermore, compounds 17a and 17d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra‐high concentration (200 μM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

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Design, synthesis and biological evaluation of amide-pyridine derivatives as novel dual-target (SE, CYP51) antifungal inhibitors

Cited by 34 publications

References 27 publications

Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

Pyridine Scaffolds, Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1‐b][1,3,4]Thiadiazole Moiety

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