Synthesis and biochemical evaluation of some novel benzoic acid based esters as potential inhibitors of oestrone sulphatase

Abstract

Oestrone sulphatase is an important target in the fight against hormone-dependent breast cancer. In an effort to investigate the reported definitive pharmacophore for oestrone sulphatase and continue our search for potent inhibitors of this enzyme, we have undertaken extensive synthesis, biochemical evaluation and physicochemical property determination of a range of benzoic acid based esters. Here, we report the initial results of our study into a series of straight chain alkyl esters of 4-sulphonylbenzoic acid. Using these compounds, we have investigated the involvement of two physicochemical properties, namely logP and pK(a). The results of this study show that there was a strong correlation between the inhibitory activity and the logP of the parent compound. Within the series of compounds studied, hydrophobicity appears to be a more important factor than pK(a) in determining the overall inhibitory activity. In a previous report, we showed that pK(a) plays an important role in stabilizing the phenoxide ion resulting from the hydrolysis of the sulphamate group. Here, we propose that although pK(a) is an important factor in determining the overall inhibitory activity when a wide range of compounds are considered, both hydrophobicity and pK(a) need to be considered in the design of potential inhibitors of oestrone sulphatase.

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

“…On the basis of 1-D, 2-D NMR and UV-Vis spectral analyses, their structures were elucidated as 1,4-dihydroxy-3,4-(epoxyethano)-5-cyclohexene (1) (Hase et al 1995) and cleroindicin E (2) (Tian et al 1997) from the dichloromethane extract, lupeol (3) (Baek et al 2010), methyl p-coumarate (4) (Chaabi et al 2010) and methyl 4-hydroxybenzoate (5) (Owen C et al 2003) from the diethyl ether extract, prunin (6) (Turner et al 2005), 5,7,2ʹ,5ʹ-tetrahydroxyflavanone 7-glucoside (7) (Aquino et al 1990), protocatechuic acid (8) (Lee et al 2011), luteolin 7-glucoside (9) (Liu et al 2012) and apigenin (10) (Owen RW et al 2003) from the ethyl acetate extract; and naringin (11) Downloaded by [Cambridge University Library] at 10:24 11 August 2015 (Yoon et al 2012), rhoifolin (12) ) and luteolin 7-glucuronate (13) (Ringl et al 2007) from the n-butanol extract. Compounds 3, 4, 5, 8, 9, 10, 11 and 12 are known antioxidant agents (Van Kiem et al 2010;Moussouni et al 2011;Hugo et al 2012;Begum & Prasad 2012;Thangavel et al 2012;Santiago & Mayor 2014;Song & Park 2014;Hlila et al 2015) and may be responsible for the significant exhibited antioxidant capacity of the diethyl ether, ethyl acetate and n-butanol extracts of the plant.…”

Antioxidant activities of natural phenolic compounds from Acacia confusa bark

“…The phenolic antioxidants of EtOAc fraction were puri-Wed and identiWed by using HPLC, MS and 1D and 2D NMR spectrometry. Eleven phenolic compounds (1-11) were isolated and identiWed as 3,4-dihydroxybenzoic acid (1) (Flamini et al, 2001) (4.3 g); 3-hydroxy-4-methoxybenzoic acid (2) (2.6 g); 3,4-dihydroxybenzoic acid methyl ester (3) (7.3 g); 3,4-dihydroxybenzoic acid ethyl ester (4) (Baderschneider and Winterhalter, 2001) (5.7 g); 4-hydroxybenzoic acid ethyl ester (5) (Owen et al, 2003) (0.9 g); 4-hydroxybenzoic acid (6) (Lo et al, 2002) (0.5 g); 4hydroxy-3,5-dimethoxybenzoic acid (7) (Hideyuki et al, 1980) (2.3 g); 4-hydroxy-3,5-dimethoxybenzoic acid ethyl ester (8) (4.3 g); 3,4-dihydroxy-trans-cinnamic acid ethyl ester (9) (Sugiura et al, 1989) (1.9 g); 3,4-dihydroxy-transcinnamic acid pentyl ester (10) (Naito et al, 1991) (0.7 g); and 4-hydroxy-3-methoxybenzoic acid (11) (Lee et al, 2004) (9.7 g). The 1 H, 13 C NMR, and MS spectral data of compounds 1-11 were in good agreement with the published values.…”

Structure-activity relationship of a series of 17 parabens and related compounds for histamine release in rat peritoneal mast cells and skin allergic reaction in guinea pigs

“…The structures, sources, and purity of the 17 parabens tested in the present study are listed (Table 1). Decylparaben, undecylparaben, octyl benzoate, octyl m-hydroxybenzoate and octyl o-hydroxybenzoate were synthesized following the method of Owen et al (2003) with some modifications, and was more than 98% pure as determined by gas chromatography. Dimethyl sulfoxide (DMSO) was purchased from Wako Pure Chemical Industries, Ltd., and all compounds used were dissolved in DMSO at a concentration of 10 -2 M. The c logP values of the 17 parabens and p-hydroxybenzoic acid tested in the present study were calculated by using Chemdraw ultra 10.0 software (Molecular Modeling and Analysis; Cambridge Soft Corporation, USA (2006)), and are listed in Table 1.…”