title: PPL catalyzed four-component PASE synthesis of 5-monosubstituted barbiturates: Structure and pharmacological properties.
abstract: Enzymatic four-component reactions are very rare although three-component enzymatic promiscuous reactions are widely reported. Herein, we report an efficient PASE protocol for the synthesis of potentially lipophilic zwitterionic 5-monosubstituted barbiturates by four component reaction of mixture of ethyl acetoacetate, hydrazine hydrate, aldehyde and barbituric acid in ethanol at room temperature. Seven different lipases were screened for their promiscuous activity towards the synthesis of 5-monosubstituted barbiturates and the lipase from porcine pancreas (PPL) found to give optimum efficiency. The zwitterionic 5-monosubstituted barbiturates with pyrazolyl ring showed promising pharmacological activity upon screening for antibacterial and apoptotic properties.
authors.affiliation: Department of Chemistry, North Eastern Hill University, Shillong 793022, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Bihani
authors.affiliation: Department of Chemistry, North Eastern Hill University, Shillong 793022, India.
authors.forename: Pranjal P
authors.initials: PP
authors.lastname: Bora
authors.affiliation: Department of Molecular Oncology, Cachar Cancer Hospital and Research Centre, Silchar, Assam 788015, India.
authors.forename: Alakesh K
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Biotechnology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India.
authors.forename: Reshita
authors.initials: R
authors.lastname: Baruah
authors.affiliation: Biotechnology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India.
authors.forename: Hari Prasanna Deka
authors.initials: HP
authors.lastname: Boruah
authors.affiliation: Department of Chemistry, North Eastern Hill University, Shillong 793022, India. Electronic address: ghanashyambez@yahoo.com.
authors.forename: Ghanashyam
authors.initials: G
authors.lastname: Bez
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001463:Barbiturates / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D055162:Biocatalysis; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008049:Lipase / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010179:Pancreas / Q000201:enzymology; D011720:Pyrazoles / Q000737:chemistry; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D001463:Barbiturates; D011720:Pyrazoles; C031280:pyrazole; D008049:Lipase; C032232:barbituric acid
keywords: Antibacterial; Apoptotic; Barbiturates; PASE; PPL; Pyrazolone; Zwitterionic