European Journal of Biomedical and Pharmaceutical Sciences

REGIO-SELECTIVE BROMINATION OF PHENOLS FROM MYRISTICA MALABARICA AND THEIR ANTI-PROLIFERATIVE ACTIVITY

Ajoy K. Bauri*, Ines Castro Dionicio, Sabine Foro and Esperanza J. Carcache de Blanco*

ABSTRACT

Chemical profiling of the methanol extract of the dry fruit rinds of Myristica malabarica has led to the isolation of a series of phenolic compounds (1-5), generically known as malabaricones A-D (1-4) and acyl phenol (5). The structures of these phenols were determined by using 1D and 2D NMR, and HRESI-MS study. The structural confirmation of them has been secured by single crystal by X-ray diffraction study. An attempt has been made to establish the structure activity of the above series of phenols by chemical transformation or by introduction of different functionalities into the parent molecules. Amongst them, bromination reaction of these phenols (1-5) is the most notable one. In this regard, these aforesaid phenols were brominated with N-bromosuccinamide (NBS) in 10% aqueous acetone as solvent over period of 12 hrs with continuous stirring by mechanical stirrer. The crude reaction products were purified by standard procedure. The structural characterization of bromophenols (6-10) has been carried out by spectroscopic methods and high-resolution electron spray ionization (HRESI) mass spectrometry. Experimental observations revealed that regio-selective bromination took place at the ortho-position of the hydroxyl group in the 2, 6-dihydroxy acyl moiety of the phenolic molecules (1-5). In vitro, anti-proliferative activity of the respective bromophenols has been evaluated on five different human cancer cell lines, including urinary bladder (HT-1376), colon (HT-29), thyroid (MDAT-32), leukaemia (BDCM) and breast cancer (MCF-7) cell lines, with paclitaxel as control in a SRB assay. Our new findings are regio-selective bromination of phenols isolated from Myristica malabarica at the 2, 6-dihydroxy acyl group using NBS and study of cell cytotoxicity activity of the respective bromophenols against the aforesaid human cancer cell lines. Bioassay results indicated that the inhibitory activity (IC50) of bromo-phenols (6-10) on aforesaid cell lines exhibited between the range of 5.5 ± 0.4 to 21.4 ± 2.2 µg/mL.

Keywords: Phenols; regio-selective bromination; their structural characterization by 1D & 2D NMR; anti-proliferative activity; SRB assay.