Leishmaniasis is an infectious disease caused by protozoan parasites of the Leishmania genus and affects more than 90 countries, especially in tropical and subtropical regions. The first treatment for these diseases involves pentavalent antimonial derivatives, which are very toxic and cause severe side effects. The other chemotherapeutic drugs used as second-line agents include different organic compound classes, such as pentamidine, which also cause severe side effects. Thus, new, safer, and efficient antileishmaniasis agents are urgently needed to control and treat these diseases. This mini review, which considered the last two decades of related research, highlighted the principal synthetic methodologies used to access amidine derivatives, focusing on more eco-friendly methods. Furthermore, the results obtained from evaluations of the anti-Leishmania activity and several molecular targets of the amidine derivatives are highlighted. 9 countries regions effects secondline second line classes pentamidine Thus new safer review research ecofriendly eco friendly methods Furthermore antiLeishmania anti

Resumen: En Uruguay la problemática de la resistencia de Rhipicephalus microplus a los acaricidas habilitados ha ido incrementando con los años, agravándose con la aparición de poblaciones multirresistentes en 2009. El objetivo del trabajo fue analizar la resistencia de 47 poblaciones de garrapatas entre los años 2017 y 2018 para cinco grupos químicos: piretroides (cipermetrina, flumetrina), organofosforados (ethion), amidinas (amitraz), fenilpirazoles (fipronil) y lactonas macrocíclicas (ivermectina), utilizando el Test de Paquete de Larvas (TLP) y una encuesta que se realizaba al responsable del establecimiento. De las 47 poblaciones analizadas 46 fueron resistentes a piretroides (46 cipermetrina, 45 flumetrina), presentando en su mayoría un alto nivel de resistencia. Todas las poblaciones muestreadas presentaron resistencia al menos a un grupo químico. El 68,1 % a tres o más grupos químicos de forma simultánea pero ninguna presentó resistencia ni susceptibilidad a los cinco analizados. Hubo poblaciones que presentaron resistencia a algunos grupos químicos que no habían sido utilizados en los establecimientos de los que fueron muestreadas. La mayoría de los predios realizaron un número mayor de tratamientos al año que el recomendado para un tratamiento generacional. Para todos los principios activos evaluados hubo poblaciones con sospechas de resistencia que no se confirmaron mediante TPL. Esto refleja las situaciones complejas que presentan hoy estos establecimientos en torno a la resistencia a los acaricidas por parte de R. microplus, que podría estar vinculada al modo, frecuencia y tiempo de uso de estos acaricidas. Así como también a su uso pero con otros fines y a los movimientos, ingresos principalmente, de animales a los predios.

Summary: Acaricide resistance of Rhipicephalus microplus tick in Uruguay means a serious problem that has been worsening through years hitting a high point with the detection of multiresistant populations on 2009. Therefore, the aim of this study was to analyze resistance for five chemical groups: pyrethroids (cypermethrin, flumethrin), organophosphates (ethion), amidines (amitraz), phenylpyrazoles (fipronil), macrocyclic lactones (ivermectin) on 47 populations between years 2017 and 2018 by using the Larval Packet Test (LPT) and a quiz made to the responsible for the farm. Results show that 46 from the 47 populations analyzed were resistant to pyrethroids (46 to cypermethrina, 45 to flumethryn). This chemical group also showed the largest number of resistant populations with a high grade of resistance. Every population showed to be resistant to at least one chemical group furthermore the 68.1 % of the populations were resistant to at least 3 chemical groups simultaneously but no population was diagnosed resistant to the 5 chemical groups analyzed neither to be susceptible to all 5 chemical groups. It stands out that there were populations resistant to some chemical groups that the farms of origin had never used. There were registered a higher number of treatments done per year to control R. microplus, than the one recommended for a generational treatment. For every active ingredient evaluated, there were suspicions of resistance that the Larval Packet Test could not confirm. This reflects the complex situation of these farms in what refers to acaricide resistance of R. microplus. This may be related to the way, frequency and time acaricides had been used on these farms, as well as using them for other purposes and also due to the impact of the income of animals infested with R. microplus from other origins.

Neste trabalho, a ciclocondensação dos precursores 7,7,7-trifluoro-4-metoxi-6-oxo-4 heptenoato de metila e 7,7,7-trichloro-4-metoxi-6-oxo-4-heptenoato de metila, a partir do ácido levulínico com amidinas [NH2CONH2, NH2CR(NH) (R = H, Me, Ph, NH2, SMe e 1H-pirazol-1-il), 5-amino-3-metil-1H-pirazol e 2-aminotiazol] para obtenção de 3-(6-trifluormetilpirimidina-4-il) propanoatos de metila com estrutura análoga a mediadores glutamatérgicos é relatada. A síntese de 3-(6-trifluormetilpirimidina-4-il)propanohidrazidas também é relatada. A versatilidade desse método foi demostrada através da síntese de quatorze 3(pirimidinil)propanoatos inéditos em rendimentos razoáveis a bons (38-92%). As estruturas moleculares dos produtos foram atribuídas com base nos dados de ressonância magnética nuclear (NMR) de ¹H e 13C e cromatografia de gases acoplada à espectrometria de massas (GC-MS).

The cyclocondensation of methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate and methyl 7,7,7-trichloro-4-methoxy-6-oxo-4-heptenoate, derived from levulinic acid with amidines [NH2CONH2, NH2CR(NH) (R = H, Me, Ph, NH2, SMe and 1H-pyrazol-1-yl), 5-amino-3-methyl1H-pyrazol and 2-aminothiazole] into pyrimidine and pyrimidine-like derivatives as a new type of glutamate-like 3-(trihalomethylatedpyrimidinyl)propanoate is reported. Preparation of 3-(trihalomethylatedpyrimidinyl) propanohydrazides is also described. The synthetic potential of this straightforward protocol was established by the synthesis of fourteen new 3-(pyrimidinyl) propanoates in regular to good yields (38-92%). The structural assignments were based on the analysis of their ¹H and 13C nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) data.

Biscationic amidines bind in the DNA minor groove and present biological activity against a range of infectious diseases. Two new biscationic compounds (bis-α,ω-S-thioureido, amino and sulfide analogues) were synthesized in good yields and fully characterized, and their interaction with DNA was also investigated. Isothermal titration calorimetry (ITC) was used to measure the thermodynamic properties of binding interactions between DNA and these ligands. A double stranded calf thymus DNA immobilized on an electrode surface was used to study the possible DNA-interacting abilities of these compounds towards dsDNA in situ. A remarkable interaction of these compounds with DNA was demonstrated and their potential application as anticancer agents was furthered.

Neste trabalho é apresentada a síntese, em rendimentos razoáveis (50-67%), de novos sistemas biheterocíclicos, duas 6-(2-heteroaril)-4-trifluormetil-2-(1H)-pirimidinonas (2a,b) e uma série de dez 6-(2-heteroaril)-4-trifluormetilpirimidinas (3a,b -7a,b) a partir da ciclocondensação de 1,1,1-trifluor-4-(2-heteroaril)-4-metoxi-3-buten-2-onas com uréia e amidinas. As estruturas de todos os compostos foram atribuídas pelos dados de análise elementar, espectrometria de massas e dados de RMN ¹H e 13C. Os dados de RMN ¹H e 13C são mostrados de maneira sistemática. Também apresentamos os dados de difração de raios-X de um monocristal da 2-amino-6-(tien-2-il)-4-trifluormetilpirimidina (5b).

The synthesis of biheterocyclic systems 6-(2-furyl)-pyrimidines and 6-(2-thienyl)pyrimidines in reasonable yields (50-67%), two 6-(2-heteroaryl)-4-trifluoromethyl-2-(1H)pyrimidinones (2a,b) and a series of ten 6-(2-heteroaryl)-4-trifluoromethylpyrimidines (3a,b 7a,b) from the cyclocondensation of 1,1,1-trifluoro-4-(2-heteroaryl)-4-methoxy-3-buten-2-ones with urea and amidines is reported. Structures of all compounds have been elucidated by elemental analysis, mass spectrometry and ¹H, 13C NMR measurements. The ¹H and 13C NMR data are systematically reported. The X-ray diffraction data for monocrystal from 2-amino-4trifluoromethyl-6-(thien-2-yl)-pyrimidine (5b) are reported.

The amidine functional group is found in a wide range of natural products and is biologically active against several pathogens. In addition, amidines have long been regarded as useful intermediates in the synthesis of heterocyclic compounds. Consequently, a great number of methods have been developed for the preparation of amidines. Pinner's method is the most commonly used. Conventional methods include: - the addition of metal amides or amines to nitriles, the addition of amines to imido esters and the condensation of amides with amines in the presence of halogenating reagents. In this report, the main methods for synthesis of amidines will be described.