title: Investigating structure-activity relationship and mechanism of action of antitubercular 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione [CD59].
abstract: OBJECTIVE
  The objective of this study is to synthesize and evaluate 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione (CD59) analogues to establish structure-activity relationship and mechanism of action.
  
  
  METHODS
  Thirty analogues of reported antitubercular CD59 were prepared by two-step synthetic protocols and characterized. The compounds were evaluated for in vitro activities against Mycobacterium tuberculosis (MTB), cytotoxicity against RAW 264.7 cells. The molecules were also evaluated for three mycobacterial enzymes to study the mechanism of action.
  
  
  RESULTS
  Among the compounds, 4-(2-bromobenzylidene)-1-(4-chlorophenyl)pyrazolidine-3,5-dione (4k) was found to be the most active compound in vitro with MICs of 4.13μM against log-phase culture of MTB and also non-toxic up to 50μM.
  
  
  CONCLUSIONS
  Amongst all, the compounds 4g, 3i and 3n were most active against the enzymes MTB Pantothenate synthetase, lysine amino transferase and Alanine dehydrogenase, respectively. Further screening of these molecules was required in the in vitro dormant MTB models.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Samala
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Shruti Singh
authors.initials: SS
authors.lastname: Kakan
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Nallangi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Parthiban Brindha
authors.initials: PB
authors.lastname: Devi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Jonnalagadda Padma
authors.initials: JP
authors.lastname: Sridevi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Saxena
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India. Electronic address: dsriram@hyderabad.bits-pilani.ac.in.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
keywords: Alanine dehydrogenase; Lysine amino transferase; Mycobacterium tuberculosis; Pantothenate synthetase