Synthesis and Evaluation of Antimicrobial Activity and Molecular Docking of New N-1,3-thiazol-2-ylacetamides of Condensed Pyrido[3',2':4,5] furo(thieno)[3,2-d]pyrimidines

Author(s): Samuel N. Sirakanyan*, Victor G. Kartsev, Athina Geronikaki*, Domenico Spinelli, Anthi Petrou, Elmira K. Hakobyan, Jasmina Glamoclija, Manija Ivanov, Marina Sokovic, Anush A. Hovakimyan

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 24 , 2020

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Graphical Abstract:


Background: From the literature it is known that many derivatives of fused thienopyrimidines and furopyrimidines possess broad spectrum of biological activity.

Objectives: The current studies describe the synthesis and evaluation of antimicrobial activity of some new N-1,3-thiazol-2-ylacetamides of pyrido[3',2':4,5]furo(thieno)[3,2-d]pyrimidines.

Methods: By cyclocondensation of ethyl 1-aminofuro(thieno)[2,3-b]pyridine-2-carboxylates 1with formamide were converted to the pyrido[3',2':4,5]furo(thieno)[3,2-d]pyrimidin-7(8)-ones 2.Alkylation of compound 2 with 2-chloro-N-1,3-thiazol-2-ylacetamide led to the aimed N-1,3-thiazol-2-ylaceta-mides of pyrido[3',2':4,5]furo(thieno)[3,2-d]pyrimidines 3. Starting from compound 2 the relevant S-alkylated derivatives of pyrido[3',2':4,5]furo(thieno)[3,2-d]pyrimidines 6 were also synthesized.

Results: All the compounds showed antibacterial activity to non-resistant strains. Compounds 3a-3m showed antibacterial activity with MIC/MBC at 0.08-2.31 mg/mL/0.11-3.75 mg/mL .The two most active compounds, 3j and 6b, appeared to be more active towards MRSA than the reference drugs. Half of the tested compounds appeared to be equipotent/more potent than ketoconazole and more potent than bifonazole.

The docking analysis provided useful information about the interactions occurring between the tested compounds and the different enzymes.

Conclusion: Gram-negative and Gram-positive bacteria and fungi showed different response towards tested compounds, indicating that different substituents may lead to different modes of action or that the metabolism of some bacteria/fungi was better able to overcome the effect of the compounds or adapt to it.

Keywords: furo(thieno)[3, 2-d]pyrimidin-7(8)-ones, furo(thieno)[3, 2-d]pyrimidin-4(7, 8)-thiones, 2-chloro-N-1, 3-thiazol 2- ylacetamide, Alkylation, Antimicrobial activity, Biological activity.

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Year: 2020
Page: [2192 - 2209]
Pages: 18
DOI: 10.2174/1568026620666200628145308
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