In vitro spermatostatic activity of mulinane- and azorellane-type diterpenes on human spermatozoa

Mulinenic acid (1), mulinolic acid (2) and azorellan- 17,13- (β) olide (3) isolated from Mulinum spinosum and Azorella trifurcata have been evaluated for their spermatostatic activity on human spermatozoa. In vitro sperm motility, viability and recovery of the motility were assessed. Compounds 2 and 3 showed significant spermatostatic properties. Reversible effects for 2 (% Motile Cells = 32 ± 3, % Living Cells = 84 ± 4) and irreversible effects for 3 (% Motile Cells = 34 ± 4, % Living Cells = 82 ± 4) were observed. Compound 1 showed moderate bioactivity. Compounds 2-3 presented remarkable effects on human sperm motility and we were encouraged to consider their application as a potential non hormonal male contraceptive agent.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Sesquiterpene lactones affect the redox system of trypanosoma cruzi

Chagas disease is caused by Trypanosoma cruzi (T. cruzi) and affects millions of people worldwide, mostly in Latin America. Despite its sanitary importance, there are currently only two drugs available for its treatment: benznidazole and nifurtimox, both exhibiting serious adverse effects on patients. In order to complete its life cycle, T. cruzi faces extreme environmental conditions ?i.e. oxidative stress- as it propagates from an insect vector to a mammalian host, driving the transition from non-infective epimastigote to the infective form trypomastigote. It is known that the antioxidant defense system in the trypanosomatids is different from that in mammalian cells since the parasites have exclusive molecules and reducing enzymes. Because of this, the parasite redox machinery is an attractive target for antiparasitic therapies. The sesquiterpene lactone dehydroleucodine (DhL), is a trypanocidal molecule containing an alpha-methylene group that could react with sulfhydryl groups of key redox enzymes. This study was focused on elucidating the DhL mechanism of action and extended to ten DhL derivatives (DC-X1 to DC-X10) obtained by chemical substitutions on the methylene group. We firstly confirmed an antiproliferative effect of DhL and its chemical derivatives, being DC- X6 one of the most active. The effect of DhL and DC-X6 was blocked by reduced glutathione, suggesting that compounds are reactive to sulfhydryl groups of certain molecules. Moreover, parasites overexpressing reducing enzymes, such as Tc-CPX, showed a protective effect against these STLs. Consistent with these results, both STLs increased ROS concentration in the wild type parasites. These results indicate that STLs induce oxidative stress on the parasites, possibly by affecting some crucial enzymes of the redox system.Fil: Gomez, Jessica Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; ArgentinaFil: Guarise, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; ArgentinaFil: Tello Faral, P.. Instituto Pasteur de Montevideo; UruguayFil: Robello, Carlos. Instituto Pasteur de Montevideo; UruguayFil: Caballero, P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; ArgentinaFil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa, M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaXXXVII Reunión Científica Anual de la Sociedad de Biología de CuyoSan LuisArgentinaSociedad de Biología de Cuy

Choleretic activity of five species of baccharis ("carquejas") used as phytotherapics in Argentinean traditional medicine

Seveal Baccharis species known as "carquejas" are used in Argentinean folk medicine as phytotherapics. B. crispa, B. articulata, B. trimera, B. sagittalis and B. triangularis have been evaluated for their choleretic activity using Wistar rats. B. sagittalis and B. triangularis showed a significant choleretic activity (bile flow of 1.631 ± 0.089 and 1.598 ± 0.196 μl/min/g liver, respectively). B. crispa, B. trimera showed moderate activity and B. articulata exhibited the same choleretic property that the control. Only, B. articulata and B. crispa are informed as official drugs in the Argentinean Pharmacopoeia. In addition, phytochemical constituents and botanical characters are reportedColegio de Farmacéuticos de la Provincia de Buenos Aire

Bioactive flavones and terpenes from Baccharis calliprinos and B. rhetinodes (Asteraceae)

El estudio fitoquímico de Baccharis calliprinos Griseb. permitió el aislamiento del ácido 2α,3α-dihidroxicativico (I) y de los flavonoides luteolina-7,3'-dimetiléter (II); homoenodictyol (III) y eriodictyol-3',4'-dimetiléter (IV). Por otra parte, de las partes aéreas de B. rhetinodes Meyen & Walp fueron aislados bacchotricuneatina A (V), ácido oleanólico (VI ) y la flavona (II). Los tres flavonoides informados, fueron sometidos al bioensayo de actividad antiinflamatoria utilizando el método del edema inducido por carragenina en pata de ratónThe chemical study of Baccharis calliprinos Griseb. yielded 2α,3α-dihydroxycativic acid (I) together with the flavonoids luteolin-7,3'-dimethylether (II), homoeriodictyol (III) and eriodictyol-3',4'- dimethylether (IV). On the other hand, from the aerial parts of B. rhetinodes Meyen & Walp bacchotri- cuneatin A (V), oleanolic acid (VI) and the flavone (II) were isolated. The three isolated flavonoids were subjected to the antiinflammatory test using the carrageenan-induced mouse paw edema test.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Bioactive flavones and terpenes from Baccharis calliprinos and B. rhetinodes (Asteraceae)

El estudio fitoquímico de Baccharis calliprinos Griseb. permitió el aislamiento del ácido 2α,3α-dihidroxicativico (I) y de los flavonoides luteolina-7,3'-dimetiléter (II); homoenodictyol (III) y eriodictyol-3',4'-dimetiléter (IV). Por otra parte, de las partes aéreas de B. rhetinodes Meyen & Walp fueron aislados bacchotricuneatina A (V), ácido oleanólico (VI ) y la flavona (II). Los tres flavonoides informados, fueron sometidos al bioensayo de actividad antiinflamatoria utilizando el método del edema inducido por carragenina en pata de ratónThe chemical study of Baccharis calliprinos Griseb. yielded 2α,3α-dihydroxycativic acid (I) together with the flavonoids luteolin-7,3'-dimethylether (II), homoeriodictyol (III) and eriodictyol-3',4'- dimethylether (IV). On the other hand, from the aerial parts of B. rhetinodes Meyen & Walp bacchotri- cuneatin A (V), oleanolic acid (VI) and the flavone (II) were isolated. The three isolated flavonoids were subjected to the antiinflammatory test using the carrageenan-induced mouse paw edema test.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Improving in the antibacterial activity and the antioxidant properties of chemically modified extracts of Zinnia peruviana

In the present work we investigate the changes in the antibacterial activity and the antioxidant properties of modified extracts of Zinnia peruviana (L.) L. campesterol, stigmasterol and β-sitosterol were identified as majortriterpenoids in the natural extract, by CG-EIMS and NIST Mass Spectrometry Data Center. The acetonic extract was chemically modified by reactions of acid hydrolysis, sulfonylation, acetylation, methylation and silylation. The in-vitro antibacterial activity was evaluated against Gram-positive and Gram-negative bacteria. The acetonic extract showed significant activity only against Gram-positive bacteria (MIC/MBC = 2/9 mg/mL). The hydrolyzed extract improve the bioactivity to both, Gram-positive and Gram-negative (MIC/MBC = 2/8 mg/mL). Selectively, the acetylated extract was only effective toward Staphylococcus (MIC/MBC = 7/7 mg/mL). The tosylated extract was active against Gram-positive and P. aeruginosa (MIC/MBC = 24/24 mg/mL) and the silylated against Grampositiveand E. coli. (MIC/MBC = 15/15 mg/mL). The antioxidant activity was determining by DPPH and ABTS assays. Hydrolyzed extract increased the antioxidant properties (DPPH, IC50,(mg/mL) = 0.077 ± 0.007; ABTS IC50,(mg/mL) = 0.032 ± 0.005). The acylated and alkylated extracts reduce the bioactivity and silylated derivative eliminated the bioactivity. These results could be considered as a possible strategy to obtain antimicrobial agents from herbal medicines.Fil: Mohamed, Ana Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Salinas, A.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Mattana, C.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Satorres, S.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Ortega, C.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Favier, L.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentin

Herbal Medicines in Central-Western Argentina

Las plantas medicinales llamadas "carquejas" (Baccharis p.p.min., Asteraceae) están caracterizadas por sus tallos áfilos y alados. Baccharis articulata y B. crispa (FNA VI ed.), y B. trimera son importantes medicamentos herbarios y fitoterápicos (hepáticos, colagogo-coleréticos y diuréticos) en la región de Cuyo, en el centro-oeste argentino. Estudios etnobotánicos recientes han permitido reconocer otras dos especies silvestres de "carquejas" con usos populares: B. sagittalis (Less.) DC., y B. triangularis Hauman de las que se comunican los constituyentes fitoquímicos y caracteres farmacobotánicos y farmacognósticos, con el objeto de brindar una adecuada definición de estas drogas y contribuir a su efectivo control de calidad.The medicinal plants called "carquejas" (Baccharis p.p.min., Asteraceae) are characterized by their aphyllous, wing-shaped stems. Baccharis articulata and B. crispa (FNA ed. VI) and B. trimera are important herbal remedies and phytotherapics (hepatics, cholagoghe-choleretics and diuretics) in Cuyo region, central-western Argentina. Recent ethnobotanic studies have allowed the addition of other two wild species of "carquejas" with popular medicinal uses: B. sagittalis (Less.) DC. and B. triangularis Hauman from which their phytochemical constituents and pharmacobotanic and pharmacognostic characters are reported with the aim to give an adequate definition of the drugs as well as contribute to their effective quality control.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Membrane fluidity adjusts the insertion of the transacylase PlsX to regulate phospholipid biosynthesis in Gram-positive bacteria

PlsX plays a central role in the coordination of fatty acid and phospholipid biosynthesis in Gram-positive bacteria. PlsX is a peripheral membrane acyltransferase that catalyzes the conversion of acyl-ACP to acyl-phosphate, which is in turn utilized by the polytopic membrane acyltransferase PlsY on the pathway of bacterial phospholipid biosynthesis. We have recently studied the interaction between PlsX and membrane phospholipids in vivo and in vitro, and observed that membrane association is necessary for the efficient transfer of acyl-phosphate to PlsY. However, understanding the molecular basis of such a channeling mechanism remains a major challenge. Here, we disentangle the binding and insertion events of the enzyme to the membrane, and the subsequent catalysis. We show that PlsX membrane binding is a process mostly mediated by phospholipid charge, whereas fatty acid saturation and membrane fluidity remarkably influence the membrane insertion step. Strikingly, the PlsXL254E mutant, whose biological functionality was severely compromised in vivo but remains catalytically active in vitro, was able to superficially bind to phospholipid vesicles, nevertheless, it loses the insertion capacity, strongly supporting the importance of membrane insertion in acyl-phosphate delivery. We propose a mechanism in which membrane fluidity governs the insertion of PlsX and thus regulates the biosynthesis of phospholipids in Gram-positive bacteria. This model may be operational in other peripheral membrane proteins with an unprecedented impact in drug discovery/development strategies.his work was supported by Ministerio de Economía, Industria y Competitividad (MINECO) Contracts BFU2016-77427-C2-2-R and BFU2017-92223-EXP, and Severo Ochoa Excellence Accreditation SEV-2016-0644 (to M. E. G.), Grant KK-2019/00076 from the Basque Government (to M. E. G.), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Postdoctoral Fellowship 2014/13411-1 (to D. E. S.), “Juan de la Cierva” post-doctoral contract IJCI-2014-19206 from the MINECO (to B. T.), FAPESP Grants 2016/05203-5 (to F. G.-F.) and 2015/21583-0 (to M. N.), FAPESP scholarship 2014/00206-0 (to L. G. M. B.), and a Career Investigator Award from Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina) (to D. d. M.).Peer reviewe