title: Monocyclic β-lactam and unexpected oxazinone formation: synthesis, crystal structure, docking studies and antibacterial evaluation.
abstract: Novel monocyclic β-lactam derivatives bearing aryl, phenyl and heterocyclic rings were synthesized as possible antibacterial agents. Cyclization of imines (3h, 3t) with phenylacetic acid in the presence of phosphoryl chloride and triethyl amine did not afford the expected β-lactams. Instead, highly substituted 1,3-oxazin-4-ones (4h, 4t) were isolated as the only product and confirmed by single crystal X-ray analysis of 4t. The results of antibacterial activity showed that compound 4l exhibited considerable antibacterial activity with MIC and MBC values of 62.5 µg/mL against Klebsiella pneumoniae. Cytotoxicity assay on Chinese Hamster Ovary (CHO) cell line revealed non-cytotoxic behavior of compounds 4d, 4h, 4k and 4l up to 200 μg/mL conc. Molecular docking was performed for compound 4l with penicillin binding protein-5 to identify the nature of interactions. The results of both in silico and in vitro evaluation provide the basis for compound 4l to be carried as a potential lead molecule in the drug discovery pipeline against bacterial infections.
authors.affiliation: a Medicinal Chemistry Lab, Department of Biosciences, Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India .|b Department of Chemistry , Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India .
authors.forename: Babita
authors.initials: B
authors.lastname: Aneja
authors.affiliation: a Medicinal Chemistry Lab, Department of Biosciences, Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India .
authors.forename: Mohammad
authors.initials: M
authors.lastname: Irfan
authors.affiliation: c Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India .
authors.forename: Md Imtaiyaz
authors.initials: MI
authors.lastname: Hassan
authors.affiliation: c Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India .
authors.forename: Amresh
authors.initials: A
authors.lastname: Prakash
authors.affiliation: d Department of Biochemistry , Albert Einstein College of Medicine of Yeshiva University , Bronx , NY , USA .
authors.forename: Umesh
authors.initials: U
authors.lastname: Yadava
authors.affiliation: e Organisch-Chemisches Institut, Westfälische Wilhelm-Universität , Münster , Germany , and.
authors.forename: Constantin G
authors.initials: CG
authors.lastname: Daniliuc
authors.affiliation: f Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India.
authors.forename: Md
authors.initials: M
authors.lastname: Zafaryab
authors.affiliation: f Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India.
authors.forename: M Moshahid A
authors.initials: MM
authors.lastname: Rizvi
authors.affiliation: b Department of Chemistry , Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India .
authors.forename: Amir
authors.initials: A
authors.lastname: Azam
authors.affiliation: a Medicinal Chemistry Lab, Department of Biosciences, Jamia Millia Islamia (A Central University) , Jamia Nagar , New Delhi , India .
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abid
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003500:Cyclization; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010080:Oxazoles; D047090:beta-Lactams
keywords: 1,3-Oxazin-4-one; antibacterial; cytotoxicity; docking; β-lactam