title: Design, synthesis and molecular docking of substituted 3-hydrazinyl-3-oxo-propanamides as anti-tubercular agents.
abstract: Based on the anti-mycobacterial activity of various acid hydrazides, a series of substituted 3-hydrazinyl-3-oxo-propanamides has been designed. The target compounds have been synthesized from diethylmalonate using substituted amines and hydrazine hydrate in ethanol. Computational studies and anti-tubercular activity screenings were undertaken to test their inhibitory effect on protein kinase PknB from Mycobacterium tuberculosis. Binding poses of the compounds were energetically favorable and showed good interactions with active site residues. Designed molecules obey the Lipinski's rule of 5 and gave moderate to good drug likeness score. Among the sixteen compounds (1-16) taken for in silico and in vitro studies, 3 compounds (11, 12 and 15) have shown good binding energies along with exhibiting good anti-tubercular activity and thus may be considered as a good inhibitors of PknB.
authors.affiliation: Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Arshi
authors.initials: A
authors.lastname: Naqvi
authors.affiliation: Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Malasoni
authors.affiliation: Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Akansha
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Rishi Ranjan
authors.initials: RR
authors.lastname: Pandey
authors.affiliation: Division of Pharmaceutics, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: anilcdri@gmail.com.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D015195:Drug Design; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000577:Amides; D000995:Antitubercular Agents; D006834:Hydrazines; C029424:hydrazine
keywords: Anti-tubercular; Binding energy; Drug likeness score; Hydrazides; Molecular docking