title: Isolation of isoflavones from Iris kashmiriana Baker as potential anti proliferative agents targeting NF-kappaB.
abstract: Cancer is possibly one of the most devastating and complex disease and therefore involves chemotherapy as one of the frontline strategies in its therapy. However, expected toxicity and resistance with chemotherapeutic agents encourage us to use the plant derived natural chemotherapeutic sources at the clinical stage of cancer therapy. In view of this strategy, herein new glycosides and isoflavonoids were isolated from Iris kashmiriana Baker and subjected to structure elucidation followed by their biological evaluation. Isolated compounds and their derivatives were purified by the column chromatography and structural identification was made by a combination of various spectroscopic technique vis. UV, IR,1H NMR,13C NMR, DEPT, 2-D NMR and mass spectrometry coupled with chemical analysis. Furthermore, an in silico library of isolated isoflavones and its analogues were designed. NF-kappaB (transcription factor that facilitates angiogenesis, inflammation, invasion and metastasis) was selected as a target to evaluate the anticancer and antioxidant activity of isoflavones and its analogues. Designed library of isoflavones and analogues were docked into the active site of NF-kappa B and the most active 15 analogues were selected for synthesis. Finally, all compounds were evaluated for their cytotoxicity against various cell lines and antioxidant activity with different methods that demonstrate their anti-cancer and anti-oxidant potential. The cell cycle specificity of the cytotoxicity was further analyzed by corresponding analysis, using flow cytometer. Most of the compounds exhibit moderate activity, whereas the 5,7,8-trihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one, 5,7,8-trihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one, 5,7,8-triacetoxyoxy-3-(4-methoxyphenyl)-4H-chromen-4-one and 6,7-diacetoxyoxy-3-(4-methoxyphenyl)-4H-chromen-4-one showed distinct broad-spectrum anticancer activity with IC50values ranges between 3.8 and 5.6 μg/mL. Cell cycle analysis indicates that these compounds induced cell cycle arrest at G2/M phase.
authors.affiliation: Faculty of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh 173229, India. Electronic address: afrozepharma@gmail.com.
authors.forename: Afroze
authors.initials: A
authors.lastname: Alam
authors.affiliation: Faculty of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh 173229, India.
authors.forename: Varun
authors.initials: V
authors.lastname: Jaiswal
authors.affiliation: LE STUDIUM(®) Loire Valley Institute for Advanced Studies, Centre-Val de Loire Region, France; Centre de Biophysique Moléculaire, CNRS UPR4301, Orléans, France.
authors.forename: Sohail
authors.initials: S
authors.lastname: Akhtar
authors.affiliation: Manipal College of Pharmaceutical Sciences, Manipal University, Udupi, Karnataka 576104, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Jayashree
authors.affiliation: Faculty of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh 173229, India. Electronic address: dharkl@yahoo.com.
authors.forename: K L
authors.initials: KL
authors.lastname: Dhar
mesh_terms: D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology; D006801:Humans; D031323:Iris Plant / Q000737:chemistry*; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects*; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D014151:Anti-Anxiety Agents; D000970:Antineoplastic Agents; D006027:Glycosides; D007529:Isoflavones; D016328:NF-kappa B
keywords: Anticancer; Antioxidants; Cell cycle analysis; Docking study; G2/M phase; Iridaceae; Iris kashmiriana Baker; Isoflavonoid; NF-kappa B