Activities of 2,4-Dihydroxy-6-n-pentylbenzoic Acid Derivatives

Abstract

Esters of 2-hydroxy-4-methoxy-6-n-pentylbenzoic acid (2-8) (methyl, ethyl, butyl, pentyl, isopropyl, sec-butyl and benzyl), olivetol (9), methyl, ethyl, butyl perlatolates (10-12), 2,4-dihydroxy-6-n-pentylbenzoic acid (15), and methyl and ethyl esters of (15) were prepared through structural modifications of perlatolic acid (1) with the aim to detect new antifungal and antibacterial substances and also to evaluate the toxicity by the brine shrimp lethality assay against Artemia salina. The antifungal assays were carried out against the fungus Cladosporium sphaerospermum through the bioautography method, and methyl 2,4-dihydroxy-6-n-pentylbenzoate (13) showed the highest antifungal activity (2.5 yg). Olivetol (9) and 2,4-dihydroxy-6-n-pentylbenzoic acid (15) are also potent inhibitors of the growth of the fungus (5.0 microg). Except for methyl (10), the ethyl (11) and butyl (12) perlatolates were less active than perlatolic acid (1). The activities presented by methyl (2) and ethyl (3) 2-hydroxy-4-methoxy-6-n-pentylbenzoates and methyl (13) and ethyl (14) 2,4-dihydroxy-6-n-pentylbenzo-ates suggest that compounds with a free hydroxy group in the aromatic ring (C-4) have a more pronounced effect against C. sphaerospermum. Antibacterial activities were tested by the disc diffusion method using pathogenic strains of S. aureus and E. coli. The compounds were weakly active with inhibition zones between 9-15 mm. The 2-hydroxy-4-methoxy-6-n-pentylbenzoic esters 2-8 and alkyl perlatolates 10-12 were selective against E. coli. Perlatolic acid (1) and methyl 2-hydroxy-4-methoxy-6-n-pentylbenzoate (2) were the most active with LD50 values of 24.1 microM and 27.2 microM, respectively. The other compounds were not toxic to Artemia salina larvae.