TY - JOUR
T1 - Isolation of isoflavones from Iris kashmiriana Baker as potential anti proliferative agents targeting NF-kappaB
AU - Alam, Afroze
AU - Jaiswal, Varun
AU - Akhtar, Sohail
AU - Jayashree, B. S.
AU - Dhar, K. L.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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 IC50 values ranges between 3.8 and 5.6 μg/mL. Cell cycle analysis indicates that these compounds induced cell cycle arrest at G2/M phase.
AB - 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 IC50 values ranges between 3.8 and 5.6 μg/mL. Cell cycle analysis indicates that these compounds induced cell cycle arrest at G2/M phase.
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U2 - 10.1016/j.phytochem.2017.01.002
DO - 10.1016/j.phytochem.2017.01.002
M3 - Article
C2 - 28108024
AN - SCOPUS:85009807565
SN - 0031-9422
VL - 136
SP - 70
EP - 80
JO - Phytochemistry
JF - Phytochemistry
ER -