Antiproliferative and Antifungal Activity of Penicillic Acid in Comparison with Its Different Derivatives

Abstract

Earlier, we have reported penicillic acid to be the major secondary metabolite from ethyl acetate extract of the broth produced by a fungal strain named as Penicillium polonicum. It exhibited high inhibitory activity against a plant pathogen Pythium aphanidermatum. In order to establish structure-activity relationship of penicillic acid, a series of chemical transformations of this constituent has been carried out under different reaction conditions, alteration of solvents and changing reagents. The yield was processed by various standard separation technique followed by preparative TLC and crystallization where it possible. The structural characterization of purified derivatives has been determined by chemical, spectral and spectrometric methods. The evaluation of antiproliferative activity of them was conducted on different human cancer cell lines. It has also been evaluated for antibiosis against P. aphanidermatum. The penicillic acid and dihydro-penicillic acid exhibited moderate activity against pancreatic (HPAC-1376), colon (HT-29) and thyroid (MDA-T32) cancer cell lines with IC₅₀ values 15.66/16.09, 18.74/18.37, and 19.18/19.17 µg/mL respectively. Unlike the parent compound and none of the derivatives viz. dihydropenicillic acid (2), bromohydroxy penicillic acid (3), dibromo-penicillic acid (4), bromosuccinmidyl-penicillic acid (5), bromohydro-penicillic acid (6), demethoxy-penicillic acid (7), sulphated-penicillic acid (8), hydroxyl penicillic acid (9), and bromo-amino penicillic acid (10) showed inhibitory activity against P. aphanidermatum.