title: Synthesis of novel spirooxindolo-pyrrolidines, pyrrolizidines, and pyrrolothiazoles via a regioselective three-component [3+2] cycloaddition and their preliminary antimicrobial evaluation.
abstract: A series of spirooxindolo-pyrrolidines, pyrrolizidines, and pyrrolothiazoles hybrid compounds were prepared in good yields by regioselective, three-component, 1,3-dipolar cycloaddition reactions between α, β-unsaturated ketones with furanyl substituents and unstable azomethine ylides, which were generated in situ from isatin and various types of amino acids. The synthesized compounds were screened for their antibacterial activities against a spectrum of pathogens. Preliminary studies identified compound 5c as a potent antimicrobial agent against drug-resistant bacteria. In addition, molecular docking studies indicated that compound 5c showed strong interactions with the active sites of lanosterol demethylase, dihydrofolate reductase, and topoisomerase II. This study provides an effective entry to the rapidly construction of a chemical library of heterocycles and compound 5c is one potent antibacterial lead for subsequent optimization.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Guansheng
authors.initials: G
authors.lastname: Wu
authors.forename: Liang
authors.initials: L
authors.lastname: Ouyang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Shi
authors.initials: S
authors.lastname: Zeng
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.forename: Fengbo
authors.initials: F
authors.lastname: Wu
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D061565:Cycloaddition Reaction; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013237:Stereoisomerism; D058886:Sterol 14-Demethylase / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: C584199:1'-(4-methoxyphenyl)-2'-(furan-2-carbonyl)-1',2',5',6',7',7a'-hexahydrospiro(indoline-3,3'-pyrrolizin)-2-one; D000900:Anti-Bacterial Agents; D007211:Indoles; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D013141:Spiro Compounds; D013844:Thiazoles; D058886:Sterol 14-Demethylase; D013762:Tetrahydrofolate Dehydrogenase; D004250:DNA Topoisomerases, Type II