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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

[ Vol. 20 , Issue. 24 ]

Author(s):

Samuel N. Sirakanyan*, Victor G. Kartsev, Athina Geronikaki*, Domenico Spinelli, Anthi Petrou, Elmira K. Hakobyan, Jasmina Glamoclija, Manija Ivanov, Marina Sokovic and Anush A. Hovakimyan   Pages 2192 - 2209 ( 18 )

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.

Affiliation:

Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of RA, 26 Azatutian Ave., Yerevan 0014, InterBioScreen, Moscow, Aristotle University of Thessaloniki, School of Pharmacy, Thessaloniki, 54124, Department of Chemistry G. Ciamician, Alma Mater Studiorum- Universita di Bologna, Via F. Selmi 2, Bologna 40126, Aristotle University of Thessaloniki, School of Pharmacy, Thessaloniki, 54124, Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of RA, 26 Azatutian Ave., Yerevan 0014, Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research Sinisa Stankovic, National Institute of Republic of Serbia, University of Belgrade, Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research Sinisa Stankovic, National Institute of Republic of Serbia, University of Belgrade, Mycological Laboratory, Department of Plant Physiology, Institute for Biological Research Sinisa Stankovic, National Institute of Republic of Serbia, University of Belgrade, Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of RA, 26 Azatutian Ave., Yerevan 0014

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