title: 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.
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 NH bond activation followed by CS bond formation leading to highly functionalized thiazolo[3,2-a]thiochromeno[4,3-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 5.3μg/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.
authors.affiliation: Department of Chemistry, National Institute of Technology, Warangal 506 004, Telangana, India.
authors.forename: Lingala
authors.initials: L
authors.lastname: Suresh
authors.affiliation: Department of Chemistry, National Institute of Technology, Warangal 506 004, Telangana, India.
authors.forename: P
authors.initials: P
authors.lastname: Sagar Vijay Kumar
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Poornachandra
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, India. Electronic address: cgkumar5@gmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Ganesh Kumar
authors.affiliation: Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India.
authors.forename: Nanubolu Jagadeesh
authors.initials: NJ
authors.lastname: Babu
authors.affiliation: Department of Chemistry, National Institute of Technology, Warangal 506 004, Telangana, India. Electronic address: gvpc2000@gmail.com.
authors.forename: G V P
authors.initials: GV
authors.lastname: Chandramouli
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D016982:Micrococcus luteus / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011743:Pyrimidines
keywords: Anti-biofilm; Antibacterial; Efficient protocol; Ionic liquid; Multicomponent reactions; Thiazolo[4,3-d]pyrimidines