Synthesis and antimicrobial activity of new 2-piperazin-1-yl-N-1,3-thiazol-2-ylacetamides of cyclopenta[c]pyridines and pyrano[3,4-c]pyridines.
2021
Аутори:
Sirakanyan, SamvelKartsev, Victor
Spinelli, Domenico
Geronikaki, Athina
Petrou, Anthi
Ivanov, Marija
Glamočlija, Jasmina
Soković, Marina
Hakobyan, Elmira
Hovakimyan, Anush
Тип документа:
Чланак у часопису (Рецензирана верзија)
,
© 2020 Deutsche Pharmazeutische Gesellschaft
Метаподаци
Приказ свих података о документуАпстракт:
In this study, we report the synthesis and antimicrobial activity of some new disubstituted piperazines. Thus, 3-chlorocyclopenta[c]pyridines and 6-chloropyrano[3,4-c]pyridine 1 under mild reaction conditions with piperazine gave the 3(6)-piperazine-substituted cyclopenta[c]pyridines and pyrano[3,4-c]pyridine 2. Furthermore, the latter, by alkylation with 2-chloro-N-1,3-thiazol-2-ylacetamide, led to the formation of the target compounds. The evaluation of the antibacterial activity revealed that 3k was the most potent compound. The most sensitive bacterium was found to be Listeria monocytogenes, whereas Staphylococcus aureus was the most resistant one. Three compounds, 3d, 3g, and 3k, were tested also against the following resistant strains: methicillin-resistant S. aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa. All three compounds appeared to be more potent than ampicillin against MRSA. Moreover, compound 3d showed a better activity than the reference drug ampicillin against P. aeruginosa, whereas 3g was more efficient against E. coli. The best antifungal activity was observed again for compound 3k. The most resistant fungi appeared to be Aspergillus fumigatus, whereas Trichoderma viride seemed the most sensitive one toward the compounds tested. Molecular docking studies on E. coli MurB, as well as on Candida albicans CYP51 and dihydrofolate reductase, were used for the prediction of the mechanisms of the antibacterial and antifungal activities, confirming the experimental results.
Кључне речи:
Alkylation; Antibacterial activity; Antifungal activity; Cyclopenta[c]pyridines; Disubstituted piperazines; Docking; pyrano[3,4-c]pyridinesИзвор:
Archiv der Pharmazie, 2021, 354, 1, e2000208-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Science Committee of the Republic of Armenia (No. 20TTWS‐1D009)
DOI: 10.1002/ardp.202000208
ISSN: 0365-6233
PubMed: 33029832
WoS: 000575803300001
Scopus: 2-s2.0-85092158600
URI
https://onlinelibrary.wiley.com/doi/10.1002/ardp.202000208http://www.ncbi.nlm.nih.gov/pubmed/33029832
https://radar.ibiss.bg.ac.rs/123456789/3916