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

• Published in: Chemistry Central journal 2018-03, Vol.12 (1), p.31-31, Article 31
• Main Authors: Zamrus, Siti Noor Hajar, Akhtar, Muhammad Nadeem, Yeap, Swee Keong, Quah, Ching Kheng, Loh, Wan-Sin, Alitheen, Noorjahan Banu, Zareen, Seema, Tajuddin, Saiful Nizam, Hussin, Yazmin, Shah, Syed Adnan Ali
• Format: Article
• Language: English
• Subjects: Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Organic and Medicinal Chemistry; Research Article
• ISSN: 1752-153X; 1752-153X
• DOI: 10.1186/s13065-018-0398-1

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 (IC 50  = 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 (IC 50  = 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 1 H 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 (2 E ,6 E )-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 (IC 50  = 3.02 ± 1.20 and 1.52 ± 0.60 µg/mL) against MCF-7 and MDA-MB-231 breast cancer cell lines.