Isolation of isoflavones from Iris kashmiriana Baker as potential anti proliferative agents targeting NF-kappaB

Afroze Alam, Varun Jaiswal, Sohail Akhtar, B. S. Jayashree, K. L. Dhar

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalPhytochemistry
Volume136
DOIs
Publication statusPublished - 01-04-2017

Fingerprint

transcription factor NF-kappa B
Isoflavones
NF-kappa B
Iris
isoflavones
Cells
neoplasms
cytotoxicity
cell cycle
Cell Cycle
Nuclear magnetic resonance
Cytotoxicity
Antioxidants
antioxidant activity
Neoplasms
therapeutics
isoflavonoids
G2 Phase
Glycosides
angiogenesis

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Plant Science
  • Horticulture

Cite this

Alam, Afroze ; Jaiswal, Varun ; Akhtar, Sohail ; Jayashree, B. S. ; Dhar, K. L. / Isolation of isoflavones from Iris kashmiriana Baker as potential anti proliferative agents targeting NF-kappaB. In: Phytochemistry. 2017 ; Vol. 136. pp. 70-80.
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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 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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Isolation of isoflavones from Iris kashmiriana Baker as potential anti proliferative agents targeting NF-kappaB. / Alam, Afroze; Jaiswal, Varun; Akhtar, Sohail; Jayashree, B. S.; Dhar, K. L.

In: Phytochemistry, Vol. 136, 01.04.2017, p. 70-80.

Research output: Contribution to journalArticle

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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

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AU - Dhar, K. L.

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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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