Seminal citrate is superior to PSA for detecting clinically significant prostate cancer.

PURPOSE: To establish whether the citrate concentration in the seminal fluid ([CITRATE]) measured by means of high-resolution nuclear magnetic resonance spectroscopy (1HNMRS) is superior to the serum prostate-specific antigen (PSA) concentration in detecting of clinically significant prostate cancer (csPCa) in men with persistently elevated PSA. MATERIALS AND METHODS: The group of patients consisted of 31 consecutively seen men with histological diagnosis of clinically localized csPCa. The control group consisted of 28 men under long-term follow-up (mean of 8.7 ± 3.0 years) for benign prostate hyperplasia (BPH), with persistently elevated PSA (above 4 ng/mL) and several prostate biopsies negative for cancer (mean of 2.7 ± 1.3 biopsies per control). Samples of blood and seminal fluid (by masturbation) for measurement of PSA and citrate concentration, respectively, were collected from patients and controls. Citrate concentration in the seminal fluid ([CITRATE]) was determined by means of 1HNMRS. The capacities of PSA and [CITRATE] to predict csPCa were compared by means of univariate analysis and receiver operating characteristic (ROC) curves. RESULTS: Median [CITRATE] was significantly lower among patients with csPCa compared to controls (3.93 mM/l vs. 15.53 mM/l). There was no significant difference in mean PSA between patients and controls (9.42 ng/mL vs. 8.57 ng/mL). The accuracy of [CITRATE] for detecting csPCa was significantly superior compared to PSA (74.8% vs. 54.8%). CONCLUSION: Measurement of [CITRATE] by means of 1HNMRS is superior to PSA for early detection of csPCa in men with elevated PSA.

Synthesis, antileishmanial activity and mechanism of action studies of novel ß-carboline-1,3,5-triazine hybrids.

A series of novel hybrids ß-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 µM. Compounds 9e and 16b were also active against amastigote forms, displaying IC50 values of 1.0 ±â€¯0.1 µM and 1.2 ±â€¯0.5 µM, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of ß-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death.

Synthesis and antitumor activity of novel 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) ß-carbolines and their Mannich bases.

A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) ß-carbolines (4a-e) and the corresponding Mannich bases 5-9(a-c) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a-e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15µM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67-3.20µM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines (5a, 5b, 6a, 6c and 9b), and ovarian (OVCAR-03) cell lines (5b, 6a, 6c, 9a, 9b and 9c). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding.

Assessment of Volatile Chemical Composition of the Essential Oil of Jatropha ribifolia (Pohl) Baill by HS-SPME-GC-MS Using Different Fibers.

The chemical composition of essential oil and volatile obtained from the roots of Jatropha ribifolia (Pohl) Baill was performed in this work. The Clevenger extractor was utilized in hydrodistillation of oil and chemical composition determined by gas chromatography coupled with mass spectrometry detector (GC-MS). The identification of compounds was confirmed by retention index (Kovats index) obtained from a series of straight chain alkanes (C7-C30) and by comparison with NIST and ADAMS library. A total of 61 compounds were identified in essential oil by GC-MS. The extraction of volatile was performed also by the use of the solid phase microextraction (SPME) with four different fibers. The essential oil extraction was extremely rapid (15 s) to avoid saturation of the fiber and the MS detector. The majority of the composition of essential oil is the terpenes: ß-pinene (major compound 9.16%), ß-vatirene (8.34%), α-gurjunene (6.98%), α-pinene (6.35%), camphene (4.34%), tricyclene (3.79%) and dehydro aromadendrene (3.52%) it and aldehydes and alcohols. Through the SPME it was possible to determine the nine volatile compounds not identified in oil 2,3,4-trimethyl-2-cyclopenten-1-one, α-phellandrene, 3-carene, trans-p-mentha-2,8-dienol, pinocamphone, D-verbenon, 1,3,3-trimethyl-2-(2-methyl-cyclopropyl)-cyclohexene, 2,4-diisocyanato-1-methylbenzene, and (6-hydroxymethyl-2,3-dimethylehenyl) methanol.

Determination by GC-MS-SIM of furanoditerpenes in Pterodon pubescens Benth.: development and validation.

The crude hydroalcoholic extract from fruits of P. pubescens is widely used because of its anti-rheumatic, antinociceptive and anti-inflammatory activities. Furanoditerpenes have a vouacapan skeleton and are involved with the pharmacological activity of the oil extracted from P. pubescens fruits. Furanoditerpenes methyl 6α-acetoxy-7ß-hydroxyvouacapan-17ß-oate and methyl 6α-hydroxy-7ß-acetoxyvouacapan-17ß-oate from P. pubescens were isolated and identified. The present study developed and validated a GC-MS-SIM method for the separation and quantification of vouacapan constituents in a semipurified extract from P. pubescens fruits. The GC-MS analyses were carried out using a system equipped with a HP-5 capillary column (30 m × 0.25 mm). Temperature program: 100°C (4°C min(-1))-270°C (5 min), injector 260°C, detector 270°C. Helium was used as the carrier gas (0.7 bar, 1 mL min(-1)). The MS was taken at 70 eV. Scanning speed was 0.5 scans s(-1), from 50 to 650. Sample volume was 1 µL. Split 1:20. Analyses for validation of methodology were conducted by GC-MS-SIM (Single Ion Monitoring), where the ions monitored were 131, 145 and 146 (between 43 and 44.5 min), 105, 145 and 197 (from 44.5 to 45.3 min) and 131, 178 and 312 (from 45.3 to 48.5 min).Validation of the analytical method was based on the following parameters: linearity, robustness, limits of detection and quantification, precision (within-day and between-day variabilities), recovery and stability. The method was linear over a range of 12.81-2.56 µÎ³µΛ(-1) of vouacapan 1, 112.78-22.56 µg mL(-1) of vouacapan 2, and 333.34-66.67 µg mL(-1) of vouacapans 3 and 4, with detection limits of 0.39, 3.45 and 9,44 µg mL(-1) and quantification limits of 1.19, 10.47 and 28.62 µg mL(-1), respectively. Recovery values were 100.69%, 97.48% and 96.98% for vouacapans 1, 2 and 3-4, respectively. Thus, the method was efficient to separate and quantify furanoditerpenes in the extract or fraction.

Synthesis, antitumor, antitrypanosomal and antileishmanial activities of benzo[4,5]canthin-6-ones bearing the N'-(Substituted benzylidene)-carbohydrazide and N-Alkylcarboxamide groups at C-2.

A series of novel benzo[4,5]canthin-6-ones, bearing the N'-(substituted benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis. The results indicated that N-methylpiperazyl-6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor activity with IC(50) values in the range of 1.15-8.46 µM for all cell lines tested. Compounds 13f and 13g bearing an N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively, showed potent activities towards both Trypanosoma cruzi and Leishmania amazonensis parasites, with IC(50) in the range of 0.4 to 16.70 µM.

pKa determinations of xanthene derivates in aqueous solutions by multivariate analysis applied to UV-Vis spectrophotometric data.

Xanthenes form to an important class of dyes which are widely used. Most of them present three acid-base groups: two phenolic sites and one carboxylic site. Therefore, the pKa determination and the attribution of each group to the corresponding pKa value is a very important feature. Attempts to obtain reliable pKa through the potentiometry titration and the electronic absorption spectrophotometry using the first and second orders derivative failed. Due to the close pKa values allied to strong UV-Vis spectral overlap, multivariate analysis, a powerful chemometric method, is applied in this work. The determination was performed for eosin Y, erythrosin B, and bengal rose B, and also for other synthesized derivatives such as 2-(3,6-dihydroxy-9-acridinyl) benzoic acid, 2,4,5,7-tetranitrofluorescein, eosin methyl ester, and erythrosin methyl ester in water. These last two compounds (esters) permitted to attribute the pKa of the phenolic group, which is not easily recognizable for some investigated dyes. Besides the pKa determination, the chemometry allowed for estimating the electronic spectrum of some prevalent protolytic species and the substituents effects evaluation.

Antitrypanosomal and antileishmanial activities of novel N-alkyl-(1-phenylsubstituted-beta-carboline)-3-carboxamides.

A series of 1-phenylsubstituted beta-carbolines containing an N-butylcarboxamide group at C-3 of beta-carboline nucleus were synthesized and evaluated in vitro against epimastigote form of Trypanosoma cruzi and promastigote form of Leishmania amazonensis. Among all compounds tested, two derivatives (2b and 2d) presented potent activity against both parasites. The most active derivative 2b showed also the higher selectivity index ratio (SI) for L. amazonensis (SI=2,084). The effect of other N-alkylcarboxamide groups at C-3, such as pyrrolidyl, N-cyclohexil and N-benzylcarboxamide on T. cruzi and L. amazonensis activity was also evaluated. Our results pointed the synthesized beta-carboline-3-carboxamide derivatives as potential compounds for new drugs for Chagas' disease and leishmaniasis' treatment.

Comparative study of the trypanocidal activity of the methyl 1-nitrophenyl-1,2,3,4-9H-tetrahydro-beta-carboline-3-carboxylate derivatives and benznidazole using theoretical calculations and cyclic voltammetry.

The cis and trans isomers of methyl 1-(m-nitro)phenyl and 1-(p-nitro)phenyl-1,2,3,4-tetrahydro-9H-beta-carboline-3-carboxylates (compounds 3a,b, 4a and b) were synthesized and evaluated in vitro against epimastigote forms of Trypanosoma cruzi. Among all of the evaluated tetrahydro-beta-carboline derivatives, the compound trans-methyl 1-(m-nitro)phenyl-1,2,3,4-9H-tetrahydro-beta-carboline-3-carboxylate (3b) was found to exhibit significant trypanocidal activity (IC(50)=22.2 microM). Theoretical studies of molecular conformations and electronic properties for the synthesized compounds and benznidazole, as well as, the cyclic voltammetric (CV) behaviors' determination were performed. A comparative study of the trypanocidal activity of the nitrophenyl-tetrahydro-beta-carbolines derivatives and benznidazole, using the results of theoretical calculations and of the cyclic voltammetry experiments, is presented.

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives.

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.