Antifungal Activity of Resveratrol Derivatives against Candida Species

trans-Resveratrol (1a) is a phytoalexin produced by plants in response to infections by pathogens. Its potential activity against clinically relevant opportunistic fungal pathogens has previously been poorly investigated. Evaluated herein are the candidacidal activities of oligomers (2a, 3–5) of 1a purified from Vitis vinifera grape canes and several analogues (1b–1j) of 1a obtained through semisynthesis using methylation and acetylation. Moreover, trans-ε-viniferin (2a), a dimer of 1a, was also subjected to methylation (2b) and acetylation (2c) under nonselective conditions. Neither the natural oligomers of 1a (2a, 3–5) nor the derivatives of 2a were active against Candida albicans SC5314. However, the dimethoxy resveratrol derivatives 1d and 1e exhibited antifungal activity against C. albicans with minimum inhibitory concentration (MIC) values of 29–37 μg/mL and against 11 other Candida species. Compound 1e inhibited the yeast-to-hyphae morphogenetic transition of C. albicans at 14 μg/mL

A two-step target binding and selectivity support vector machines approach for virtual screening of dopamine receptor subtype-selective ligands

10.1371/journal.pone.0039076PLoS ONE76

2-[(4-Phenylpiperazin-1-yl)methyl]imidazo(di)azines as Selective D4-Ligands. Induction of Penile Erection by 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]imidazo[1,2-a]pyridine (PIP3EA), a Potent and Selective D4 Partial Agonist

A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza-analogues were prepared and screened at selected dopamine, serotonin, and adrenergic receptor subtypes. 2-Substituted imidazopyridines and pyridazines presented high affinities and selectivities for D4 dopamine receptors. Whereas functional experiments indicated neutral antagonists or weak partial agonist effects for most of the target compounds, the 2-methoxyphenyl substituted 2-piperazinylmethylimidazopyridine 3c (PIP3EA) displayed substantial agonist efficacy in mitogenesis experiments and GTPgammaS binding tests, resulting in EC50 values of 3.0 (46%) and 4.5 nM (57%), respectively. Our D4 agonist 3c induced penile erection in vivo when administered to rats. This effect was inhibited by L-745,870 a D4 selective antagonist, confirming the mechanistic pathway

PIP3EA and PD168077, two selective dopamine D4 receptor agonists, induce penile erection in male rats: site and mechanism of action in the brain

PIP3EA (2-[4-(2-methoxyphenyl)piperazin-1-yl-methyl]imidazo[1,2-a]pyridine) and PD-168077 (N-[4-2-cyanophenylpiperazin-1-ylmethyl]-3-methylbenzamide maleate), two selective dopamine D4 agonists, administered systemically, intracerebroventricularly or into the paraventricular nucleus of the hypothalamus induce penile erection in male Sprague-Dawley rats. A U-inverted dose-response curve was found with either compound when given subcutaneously (1-100 microg/kg) or intracerebroventricularly (0.1-20 microg/rat), but not into the paraventricular nucleus (10-200 ng/rat). The pro-erectile effect of PIP3EA and of PD-168077 occurs concomitantly with an increased nitric oxide (NO) production in the paraventricular nucleus, as measured by the increased concentration of nitrites and nitrates found in the dialysate obtained from the paraventricular nucleus by intracerebral microdialysis. These effects of PIP3EA and PD-168077 were reduced by L-745,870 (3-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-1H-pyrrolo[2,3-b]pyridine trihydrochloride), a selective dopamine D4 receptors antagonist, by omega-conotoxin, a blocker of voltage-dependent Ca2+ channels of the N-type, by S-methyl-thiocitrulline, a neuronal nitric oxide synthase inhibitor, and by d(CH2)5Tyr(Me)2-Orn8-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles, but not into the paraventricular nucleus. Comparison of the dose-response curves of PIP3EA and PD-168077 revealed that PIP3EA is as potent as PD-168077 when given into the paraventricular nucleus, but more potent when given systemically. However, both compounds are less efficacious (e.g. induce a lower number of penile erection episodes) than apomorphine, a classical mixed dopamine receptor agonist, irrespective of the route of administration. These results confirm previous findings showing that central D4 receptors mediate penile erection and show that dopamine D4 receptor agonists act in the paraventricular nucleus to facilitate penile erection by increasing central oxytocinergic neurotransmission

Antioxidative and wound healing properties of Crateva adansonii

International audienc

Antioxidative and whound healing properties of <em>Crateva adansonii</em> DC

National audienc

Two biflavonoids from Ouratea nigroviolacea

The leaves of Ouratea nigroviolacea (Ochnaceae) afforded two biflavonoids, ouratine A and B together with agathisflavone and stigmasterol. The biflavonoids were characterized as 4'-O-methylated apigeninyl-(I-6, II-8)-4'-O-methylatedapigenin and 4'-O-methylated apigeninyl-(I-6, II-8) apigenin by spectral and chemical transformation studies

Antioxidative and wound healing properties of Crateva adansonii DC

Leaves of Crateva adansonii DC, a small bush found in Togo, are widely used in traditional medicine to cure infectious abscess. Traditional healers harvest only young leaves and sprouts early in the morning in order to prepare their drugs. To validate this ancestral practice, we performed a phytochemical screening of various C. adansonii leaves samples collected in different places, at different time and at different ages. Using antioxidant activity as selection criteria, optimal extracts were obtained with sprout leaves, collected at 5:00 am in Djidjolé. Wound healing potential was then investigated for several extracts in vitro on keratinocytes stimulated by Staphylococcus aureus proteins. Anti-inflammatory activity was highlighted with flavonoids-rich extracts, especially against TNFa. Those results validate the traditional practices and the potential of C. adansonii as wound healing drug