Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines

Background Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies. Results Twenty-four curcumin derivative...

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Main Authors: Zamrus, Siti Noor Hajar, Akhtar, Muhammad Nadeem, Yeap, Swee Keong, Quah, Ching Kheng, Loh, Wan-Sin, Mohammed Alitheen, Noorjahan Banu, Zareen, Seema, Tajuddin, Saiful Nizam, Hussin, Yazmin, Ali Shah, Syed Adnan
Format: Article
Language:English
Published: SpringerOpen 2018
Online Access:http://psasir.upm.edu.my/id/eprint/72196/
http://psasir.upm.edu.my/id/eprint/72196/1/Design%2C%20synthesis%20and%20cytotoxic%20effects%20of%20curcuminoids%20.pdf
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author Zamrus, Siti Noor Hajar
Akhtar, Muhammad Nadeem
Yeap, Swee Keong
Quah, Ching Kheng
Loh, Wan-Sin
Mohammed Alitheen, Noorjahan Banu
Zareen, Seema
Tajuddin, Saiful Nizam
Hussin, Yazmin
Ali Shah, Syed Adnan
author_facet Zamrus, Siti Noor Hajar
Akhtar, Muhammad Nadeem
Yeap, Swee Keong
Quah, Ching Kheng
Loh, Wan-Sin
Mohammed Alitheen, Noorjahan Banu
Zareen, Seema
Tajuddin, Saiful Nizam
Hussin, Yazmin
Ali Shah, Syed Adnan
author_sort Zamrus, Siti Noor Hajar
building UPM Institutional Repository
collection Online Access
description Background Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies. Results Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1–10, acetone 11–17 and cyclopentanone 18–24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1–24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11–17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed 1H NMR, IR, UV–Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure–activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases. Conclusions Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.
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spelling upm-721962022-06-29T07:26:01Z http://psasir.upm.edu.my/id/eprint/72196/ Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines Zamrus, Siti Noor Hajar Akhtar, Muhammad Nadeem Yeap, Swee Keong Quah, Ching Kheng Loh, Wan-Sin Mohammed Alitheen, Noorjahan Banu Zareen, Seema Tajuddin, Saiful Nizam Hussin, Yazmin Ali Shah, Syed Adnan Background Curcumin is one of the leading compound extracted from the dry powder of Curcuma longa (Zingiberaceae family), which possess several pharmacological properties. However, in vivo administration exhibited limited applications in cancer therapies. Results Twenty-four curcumin derivatives have synthesized, which comprises cyclohexanone 1–10, acetone 11–17 and cyclopentanone 18–24 series. All the curcuminoids were synthesized by the acid or base catalyzed Claisen Schmidt condenstion reactions, in which β-diketone moiety of curcumin was modified with mono-ketone. These curcuminoids 1–24 were screened against HeLa, K562, MCF-7 (an estrogen-dependent) and MDA-MB-231 (an estrogen-independent) cancer cell lines. Among them, acetone series 11–17 were found to be more selective and potential cytotoxic agents. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. Among the cyclohexanone series, the compound 4 exhibited (IC50 = 11.04 ± 2.80, 6.50 ± 01.80, 8.70 ± 3.10 and 2.30 ± 1.60 µg/mL) potential cytotoxicity against four proposed cancer cell lines, respectively. All the curcucminoids were characterized with the detailed 1H NMR, IR, UV–Vis, and mass spectroscopic techniques. The structure of compound 4 was confirmed by using the single X-ray crystallography. Additionally, we are going to report the first time spectral data of (2E,6E)-2,6-bis(2-methoxybenzylidene)cyclohexanone (1). Structure–activity relationships revealed that the mono-carbonyl with 2,5-dimethoxy substituted curcuminoids could be an essential for the future drugs against cancer diseases. Conclusions Curcuminoids with diferuloyl(4-hydroxy-3-methoxycinnamoyl) moiety with mono carbonyl exhibiting potential cytotoxic properties. The compound 14 was exhibited (IC50 = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines. SpringerOpen 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/72196/1/Design%2C%20synthesis%20and%20cytotoxic%20effects%20of%20curcuminoids%20.pdf Zamrus, Siti Noor Hajar and Akhtar, Muhammad Nadeem and Yeap, Swee Keong and Quah, Ching Kheng and Loh, Wan-Sin and Mohammed Alitheen, Noorjahan Banu and Zareen, Seema and Tajuddin, Saiful Nizam and Hussin, Yazmin and Ali Shah, Syed Adnan (2018) Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines. Chemistry Central Journal, 12 (1). art. no. 13. 31 - 40. ISSN 1752-153X https://bmcchem.biomedcentral.com/articles/10.1186/s13065-018-0398-1 10.1186/s13065-018-0398-1
spellingShingle Zamrus, Siti Noor Hajar
Akhtar, Muhammad Nadeem
Yeap, Swee Keong
Quah, Ching Kheng
Loh, Wan-Sin
Mohammed Alitheen, Noorjahan Banu
Zareen, Seema
Tajuddin, Saiful Nizam
Hussin, Yazmin
Ali Shah, Syed Adnan
Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
title Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
title_full Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
title_fullStr Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
title_full_unstemmed Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
title_short Design, synthesis and cytotoxic effects of curcuminoids on HeLa, K562, MCF-7 and MDA-MB-231 cancer cell lines
title_sort design, synthesis and cytotoxic effects of curcuminoids on hela, k562, mcf-7 and mda-mb-231 cancer cell lines
url http://psasir.upm.edu.my/id/eprint/72196/
http://psasir.upm.edu.my/id/eprint/72196/
http://psasir.upm.edu.my/id/eprint/72196/
http://psasir.upm.edu.my/id/eprint/72196/1/Design%2C%20synthesis%20and%20cytotoxic%20effects%20of%20curcuminoids%20.pdf