title: 3,4-Dihydropyrimidinone-coumarin analogues as a new class of selective agent against S. aureus: Synthesis, biological evaluation and molecular modelling study.
abstract: Bacterial infections are increasingly difficult to combat as bacteria evolve resistance to antibiotic drugs and have severely compromised the arsenal of antibiotic drugs. On the other hand matrix metalloproteinases (MMPs) play a fundamental role in inflammation and extracellular matrix degradation in physiological and pathological conditions. In search of potent antibiotic, taking coumarin and dihydropyrimidinone as lead compound, a green, eco-friendly and efficient protocol has been developed and synthesized the dihydropyrimidin-2(1H)-one/thione derivatives of coumarin 3/4 from substituted 4-formylcoumarins 2 and ethylacetoacetate using urea/thiourea in the presence of catalytic amount of ceric ammonium nitrate is reported. All the synthesized compounds were evaluated for their antibacterial activity against four bacterial strains by broth dilution method. The tested compounds have exhibited promising in vitro potency with low MIC values against the drug susceptive S. aureus strain with low MIC values ranging from 0.2 to 6.25μg/mL. The in vivo anti-inflammatory potency of 3a-e and 4a-e by gelatin zymography is comparable to that of tetracycline. Molecular docking study performed for all the synthesized compounds with S. aureus DNA gyrase and results obtained were quite promising.
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India.
authors.forename: Nirmala S
authors.initials: NS
authors.lastname: Naik
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India. Electronic address: drlashastri@kud.ac.in.
authors.forename: Lokesh A
authors.initials: LA
authors.lastname: Shastri
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580002, Karnataka, India.
authors.forename: Shrinivas D
authors.initials: SD
authors.lastname: Joshi
authors.affiliation: Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580002, Karnataka, India.
authors.forename: Sheshagiri R
authors.initials: SR
authors.lastname: Dixit
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India.
authors.forename: Bahubali M
authors.initials: BM
authors.lastname: Chougala
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India.
authors.forename: S
authors.initials: S
authors.lastname: Samundeeswari
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India.
authors.forename: Megharaj
authors.initials: M
authors.lastname: Holiyachi
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India.
authors.forename: Farzanabi
authors.initials: F
authors.lastname: Shaikh
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Madar
authors.affiliation: Department of Chemistry, Karnatak University, Dharwad 580 003, Karnataka, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: Department of Chemistry, G.S.S. College, Belagavi, Karnataka, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Sunagar
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D003374:Coumarins; D011744:Pyrimidinones
keywords: Coumarin; DNA gyrase; Gelatin zymography; Matrix metalloproteinases; S. aureus