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

• Published in: Current topics in medicinal chemistry Vol. 20; no. 24; p. 2192
• Main Authors: Sirakanyan, Samuel N, Kartsev, Victor G, Geronikaki, Athina, Spinelli, Domenico, Petrou, Anthi, Hakobyan, Elmira K, Glamoclija, Jasmina, Ivanov, Manija, Sokovic, Marina, Hovakimyan, Anush A
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2020
• Subjects: Alkylation; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemical synthesis; Biofilms - drug effects; Drug Design; Humans; Microbial Sensitivity Tests; Molecular Conformation; Molecular Docking Simulation; Protein Binding; Pyrimidines - chemistry; Pyrimidines - pharmacology; Structure-Activity Relationship; Triazoles - chemistry; Triazoles - pharmacology; Antimicrobial activity; 2-chloro-N-1; furo(thieno); 8)-thiones; 3-thiazol 2- ylacetamide; 2-d]pyrimidin-7-ones; 2-d]pyrimidin-4; Alkylation; Biological activity
• ISSN: 1873-4294

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