Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.
A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.
Department of Chemistry, Allama Iqbal Open University, H-8, Islamabad, Pakistan; Department of Biology, College of Natural Sciences, Kongju National University, Kongju, South Korea.
Zaman
Z
Ashraf
Department of Chemistry, Allama Iqbal Open University, H-8, Islamabad, Pakistan.
Abdul
A
Bais
Department of Chemistry, Kongju National University, Gongju, Republic of Korea.
Md Maniruzzaman
MM
Manir
Atta ur Rehman School of Modeling and Simulation, National University of Science and Technology, Islamabad, Pakistan.
Umar
U
Niazi
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D046915:Penicillin-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D010406:Penicillins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
D000890:Anti-Infective Agents; D046915:Penicillin-Binding Proteins; D010406:Penicillins