Synthesis and structural elucidation of two new series of aurone derivatives as potent inhibitors against the proliferation of human cancer cells

• Published in: Medicinal chemistry research 2015-09, Vol.24 (9), p.3504-3515
• Main Authors: Elhadi, Aboubaker A., Osman, Hasnah, Iqbal, Muhammad Adnan, Rajeswari, Sharmila K., Ahamed, Mohamed B. Khadeer, Abdul Majid, Amin M.S., Rosli, Mohd Mustaqim, Razak, Ibrahim Abdul, Majid, Aman Shah Abdul
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Original Research; Pharmacology/Toxicology
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-015-1400-2

Two new series of aurone compounds were synthesized via an oxidative cyclization reaction of 2′-hydroxy-chalcones. Series ( A ) consists of 1a – 3a aurones with different substitutions on a B-ring at position 4′, and series ( B ) is made up of 1b – 3b aurones that have different substitutions at position 2′ of a B-ring. Structures of the synthesized compounds were characterized and confirmed by FTIR (1D and 2D NMR) and EI mass spectral studies. The molecular structure of 2b was further confirmed by the X-ray crystallographic technique, with the compound found to be in Z -isomeric form. The compounds of both series were tested for their antiproliferative activity against human colorectal tumor (HCT 116), human chronic myelogenous leukemia (K562) and hormone-dependent breast cancer (MCF-7) cell lines according to an MTT assay. Series ( B ) exhibited a higher cytotoxic effect on the cancer cell lines compared to series ( A ). Selectively, the most promising results have been shown by the two most active compounds, 1b ( Z -5,7, 2′-trichloro-aurone), which resulted in IC 50 values of 36, 23 and 23 μM against HCT 116, MCF-7 and K562 cancer cells, respectively. Compound 3a ( Z -5, 7-dichloro-4′-methyl-aurone) exhibited the highest activity against the K562 cell line (IC 50  = 20 μM), which can be compared to that of the standard drug, betulinic acid, with an IC 50 value of 15 μM. The results of the present study suggested that aurone derivatives emerged as a potential candidate for the development of future chemotherapeutic agents.