title: Brine shrimp lethality assay 'an effective prescreen': microwave-assisted synthesis, BSL toxicity and 3DQSAR studies-based designing, docking and antitumor evaluation of potent chalcones.
abstract: BACKGROUND
  In the course of searching potential antitumor agents from a library of chalcones synthesized under microwave irradiations, the brine shrimp lethality (BSL) assay and a 3D structure-activity relationship (3DQSAR) studies were followed by the antitumor evaluation of most potent analogues.
  
  
  OBJECTIVE
  The objective of the current study was to effectively use the BSL assay for the identification of potential cytotoxic analogues from a set of compounds.
  
  
  METHODS
  We applied the comparative molecular field analysis (CoMFA) and devised 3DQSAR on 33 synthesized chalcones leading to prediction of five related compounds with improved activity. The scope of BSL assay for the prediction of antitumor potency was tested through the in vitro antitumor studies against six human tumor cell-lines, docking studies and the tubulin-polymerization assay.
  
  
  RESULTS
  The newly designed compounds 34-38 displayed very promising cytotoxic potency. From our results, the BSL toxicity, antitumor efficacy and docking outcomes could be easily co-related.
  
  
  CONCLUSIONS
  The study draws a very good relationship between a simple, inexpensive, and bench-top BSL assay and the antitumor potential of the cytotoxic compounds. Devising the CoMFA analysis helped in designing chalcones with improved cytotoxic potential as displayed through their BSL and cytotoxic activity against human tumor cell lines. The studies are noteworthy as such comprehensive studies were never performed before on the BSL assay. The present studies widen the scope of the BSL model that may prove quite helpful as a preliminary screen in the antitumor drug designing and synthesis expeditions.
authors.affiliation: NanoScience and Catalysis Division, National Centre for Physics, Quaid-i-Azam University Campus, Islamabad, Pakistan. seegasami01@yahoo.com
authors.forename: Samina
authors.initials: S
authors.lastname: Nazir
authors.forename: Farzana Latif
authors.initials: FL
authors.lastname: Ansari
authors.forename: Tajammul
authors.initials: T
authors.lastname: Hussain
authors.forename: Kehkashan
authors.initials: K
authors.lastname: Mazhar
authors.forename: Ambreen Gul
authors.initials: AG
authors.lastname: Muazzam
authors.forename: Zaheer-ul-Haq
authors.initials: ZU
authors.lastname: Qasmi
authors.forename: Talat
authors.initials: T
authors.lastname: Makhmoor
authors.forename: Humera
authors.initials: H
authors.lastname: Noureen
authors.forename: Bushra
authors.initials: B
authors.lastname: Mirza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D001156:Artemia / Q000187:drug effects; D001185:Artificial Intelligence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D019295:Computational Biology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005103:Expert Systems; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D008872:Microwaves; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy*; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D054852:Small Molecule Libraries; D014404:Tubulin; D050257:Tubulin Modulators