title: Cytotoxicity and Anti-inflammatory Activity of Flavonoid Derivatives Targeting NF-kappaB.
abstract: BACKGROUND
  Nuclear factor-kappaB (NF-kappaB) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs inhibiting NF-kappaB may possess both anti-inflammatory and anticancer properties. So there is a need to discover novel compounds which should not only be a potential lead but also less toxic and cost effective.
  
  
  OBJECTIVE
  The aim of the study was to develop new synthetic anti-inflammatory and cytotoxic agents targeting NF-kappaB.
  
  
  METHODS
  Test compounds were synthesized and characterized by UV, IR, 1H-NMR, 13C-NMR and mass spectrometry. The synthesized compounds were evaluated for in vitro cytotoxicity by MTT assay against various cancer cell lines and in vivo anti-inflammatory in carrageenan-induced paw edema model. Selected compounds were subjected to cell cycle analysis using propidium iodide. Docking study was done into an active site of NF-kappaB using Auto Dock 4.2.
  
  
  RESULTS
  Three series of compounds were synthesized and characterized by various spectroscopic techniques. The test compounds (10b), (1c) and (2c) were found to be the most potent anti-inflammatory agents, whereas compounds such as (10b), (6b), (4b), (2b), (6a), (4a), (5c) and (3c) have shown promising cytotoxicity in different cancer cell lines, followed by cell cycle analysis of selected compounds ((10b) and (4b)). The free energy of binding of ligands was in the range between -6.47 to -12.50.Kcal/ mole.
  
  
  CONCLUSIONS
  compound (10b) was found to be the most potent as both anti-inflammatory and cytotoxic agents. In silico approach was in good tune with the wet lab experiments. The promising compounds have shown to induce cell cycle arrest at G2/M Phase.
authors.affiliation: Nandha College of Pharmacy, Perundurai Main Road, Erode, Tamil Nadu-638052. India.
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Naik
authors.affiliation: School of Pharmaceutical Sciences, Shoolini University, Bajhol, Solan-173229, (Himachal Pradesh). India.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Thangavel
authors.affiliation: School of Pharmaceutical Sciences, Shoolini University, Bajhol, Solan-173229, (Himachal Pradesh). India.
authors.forename: Afroze
authors.initials: A
authors.lastname: Alam
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015195:Drug Design; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D013058:Mass Spectrometry; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010330:Patents as Topic; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D005419:Flavonoids; D016328:NF-kappa B
keywords: Anti-inflammatory; G2/M phase; cell cycle analysis; cytotoxicity; flavanone; nuclear factor-kappaB