Synthesis and highly potent anti-inflammatory activity of licofelone- and ketorolac-based 1-arylpyrrolizin-3-ones

Antifungal activity of fibrate-based compounds and substituted pyrroles inhibiting the enzyme 3-hydroxy-methyl-glutaryl-CoA reductase of Candida glabrata (CgHMGR), and decreasing yeast viability and ergosterol synthesis

“…The fibrate-based derivates 1a - c, 2a - c and 3a - c , and 1,2-dihydroquinolines 4a - d , constituted the first two series of compounds [11] (Figure 5). The substituted pyrrole derivatives comprised the third series, being 5a-d and 6b-d [12] (Figure 6). The brominated pyrroles 5b, 5c and 6b-d were designed because of its similarity to some pyrrole-based marine alkaloids known to exert both antifungal and antibacterial activity [13, 23-24].…”

“…The synthesis of 5a, 5d and 6c-d has been previously reported [11,12]. The preparation of bromopyrroles 5b and 5c was achieved by treatment of compound 5a [12] with N -bromosuccinimide (NBS) as the brominating agent under mild reaction conditions (Scheme 1). Even though l.0 mol equivalent of NBS was employed, a mixture of bromopyrroles 5b and 5c was obtained.…”

“…The synthesis of dibromopyrrole 6b was carried out by a two-step methodology. The first step consisted of a Knoevenagel reaction of 5a with malononitrile under acid conditions [12] to provide 6a in high yield (Scheme 1). Bromination of the latter with NBS (2.0 mol equiv.)…”

“…The aim of the present study was to evaluate the capacity of new synthetic compounds to inhibit the C. glabrata HMGR enzyme (CgHMGR) and therefore affect ergosterol synthesis and yeast viability. Two series of compounds were derived from fibrate-based acyl- and alkyl-phenoxyacetic methyl esters, and 1,2-dihydroquinolines [11] and a third series from substituted pyrroles [12,13]. The best compound in each series was subjected to in vitro experiments to assess yeast growth, the level of ergosterol, and yeast growth rescue with the addition of exogenous ergosterol.…”

Antifungal Activity of Fibrate-Based Compounds and Substituted Pyrroles That Inhibit the Enzyme 3-Hydroxy-methyl-glutaryl-CoA Reductase of Candida glabrata (CgHMGR), Thus Decreasing Yeast Viability and Ergosterol Synthesis

“…Two series of compounds were derived from fibrate-based acyl- and alkyl-phenoxyacetic methyl esters, as well as 1,2-dihydroquinolines ( 11 ). A third series was developed from substituted pyrroles ( 12 , 13 ). The best compound in each series was subjected to in vitro experiments to assess yeast growth, the level of ergosterol, and yeast growth rescue with the addition of exogenous ergosterol.…”