An expeditious four-component domino protocol for the synthesis of novel thiazolo[3,2-a]thiochromeno[4,3-d]pyrimidine derivatives as antibacterial and antibiofilm agents |
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| Institution: | 1. Department of Chemistry, National Institute of Technology, Warangal 506 004, Telangana, India;2. Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, India;3. Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India;1. Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India;2. Piramal Enterprise Ltd, Plot No.-18, Pharmez, Matoda Village, Ahmedabad, India;3. Department of Botany, Bioinformatics and Climate Change Impacts Management, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India;4. Microcare Laboratory & Tuberculosis Research Centre, Surat, Gujarat, India;5. Genxplore Diagnostic and Research Centre Pvt. Ltd., Ahmedabad, Gujarat, India;1. Laboratory of Medicinal Chemistry, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Quartier Hôpital B36 Av. Hippocrate, 15 B-40 0 0 Liège, Belgium;2. Unidade de Difracción de Raios X, RIAIDT, Universidade de Santiago de Compostela, Campus VIDA, 15782 Santiago de Compostela, Spain;3. Laboratory of Macromolecular Chemistry and Organic Catalysis, Department of Chemistry, University of Liège, Sart-Tilman (B.6a), Liège 4000, Belgium;1. Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;1. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Junín 954 CP 1113, Buenos Aires, Argentina;2. ISOF, Consiglio Nazionale delle Ricerche, Via P. Gobetti 101, 40129, Bologna, Italy |
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| Abstract: | An efficient domino protocol has been developed for the synthesis of new pyrimidine scaffolds, through a one-pot four-component cascade transformation via Bmim]HSO4 ionic liquid mediated reaction, using an equimolar mixture of thiochroman-4-one, benzaldehyde, thiourea and 3-bromo-1-phenylpropan-1-one leading to the formation of a double electrophilic pyrimidine-2(5H)-thione intermediate. The intermediate regioselectively undergoes cyclization through intramolecular N H bond activation followed by CS bond formation leading to highly functionalized thiazolo3,2-a]thiochromeno4,3-d]pyrimidines. The ionic liquid operates efficiently under mild conditions. The recyclability and scope for recovery of the ionic liquid makes this protocol environmentally benign. Further, the compounds 5d, 5g and 5k showed promising antimicrobial activity against the tested Gram-positive bacterial strains. Among them, the compound 5d was identified as a lead molecule exhibiting promising anti-biofilm activity towards Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Staphylococcus aureus MLS16 MTCC 2940 and Micrococcus luteus MTCC 2470 with IC50 values of 2.1, 1.9, 2.4 and 5.3 μg/mL, respectively. Further, the compound 5d showed increased levels of intracellular ROS accumulation in Staphylococcus aureus MTCC 96 suggesting that oxidative stress resulted in bacterial cell lysis and death. |
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| Keywords: | Ionic liquid Efficient protocol Multicomponent reactions Antibacterial Anti-biofilm |
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