Thiadiazine Derivatives as Antiprotozoal New Drugs

The 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione scaffold have found many applications in recent years. This review is aimed at highlighting the most important aspects about these compounds: synthesis, spectroscopic characterization and antiprotozoan activities. How the chemical nature of N-substituents influences the overall activity / cytotoxicity profile will also be discussed

Diastereoselective Synthesis of C60/Steroid Conjugates

The design and synthesis of fullerene–steroid hybrids by using Prato’s protocol has afforded new fullerene derivatives endowed with epiandrosterone, an important naturally occurring steroid hormone. Since the formation of the pyrrolidine ring resulting from the 1,3-dipolar cyloaddition reaction takes place with generation of a new stereogenic center on the C2 of the five-membered ring, the reaction proceeds with formation of a diastereomeric mixture [compounds 6 and 7 in 70:30 ratio, 8 and 9 in 26:74 ratio (HPLC)] in which the formation of the major diasteroisomers 6 and 9 is consistent with an electrophilic attack of [60]fullerene on the Re face of the azomethine ylide directed by the steroidic unit. The chiroptical properties of these conjugates reveal typical Cotton effects in CD spectra that have been used to assign the absolute configuration of the new fulleropyrrolidines. The electrochemical study of the new compounds reveals the presence of four quasi-reversible reduction waves which are cathodically shifted in comparison with the parent C60, thus ascertaining the proposed structures.Financial support by the Ministerio de Ciencia e Innovación (MINECO) of Spain (CTQ2011-24652, CTQ2011-27253, PIB2010JP-00196, and CSD2007-00010 projects) and CAM (Madrisolar-2) is acknowledged; A.R. thanks UCM for financial support; M.S. is indebted to Programa del Grupo Santander 2012

Dextran as carrier for controlled release drugs

Se presenta una revisión sobre el uso del dextrano como soporte para la dosificación controlada de fármacos, con el objetivo de mostrar las tendencias actuales en esta temática. Se exponen las características generales de los sistemas de liberación controlada y los usos específicos del dextrano como soporte de estos sistemas.The present lrends in the use of dextran as carrier for the controlled dosification of pharmaceuticals are presented. The general characteristics of the controlled release systems and the dextran specific uses as carrier for these systems are discussed.Colegio de Farmacéuticos de la Provincia de Buenos Aire

High-throughput preparation of alkyl 4-aryl substituted-2-methyl-6-thioxo-1,4,5,6-tetrahydropyridine-3-carboxylates under microwave irradiation

17 p.-1 fig.-2 tab.An efficient high-throughput synthesis of 4-aryl substituted 1,4,5,6-tetrahydro-2-methyl-6-thioxopyridine-3-carboxylates 5a-p was developed by using Lawesson’s reagent, a very effective thionating reagent for carbonyl compounds, under conventional conditions and microwave irradiation. In order to gain a better understanding of the structure of the heterocycles obtained, theoretical calculations at the ab initio level were carried out.The part of this work carried out in Barcelona was partially supported by CICYT (CTQ2009-07758), the Generalitat de Catalunya (2009SGR 1024), the Institute for Research in Biomedicine, and the Barcelona Science Park. This work was also supported by the MICINN of Spain (project CT2008-00795/BQU and Consolider-Ingenio 2010C-07-25200).Peer reviewe

Alkyl-linked bis-THTT derivatives as potent in vitro trypanocidal agents.

The effect of several alkyl-linked bis tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (bis-THTT) on Leishmania donovani, Trypanosoma brucei rhodesiense, and Plasmodium falciparum is reported. Most of the compounds exhibited a potent activity against the three parasitic strains but the best in vitro activity profiles were found against T. b. rhodesiense with IC(50) values ranging between 0.3 and 4 microM for the most active compounds

High open circuit voltage in efficient thiophene-based small molecule solution processed organic solar cells

International audienceWe have synthesized and fully characterized an oligothiophene small organic molecule for its use as electron donor moiety in solution processed bulk-heterojunction organic solar cells. Our results show that device solvent annealing process of the conjugated oligothiophene molecule leads to a light-to-energy conversion efficiency of 3.75% under standard illumination conditions. The solar cell presents open-circuit voltage and fill factors as high as 1.01 V and 63.05% respectively, which are among the highest values obtained for small molecule solution processed organic solar cells

Serological Cross-Reaction between Six Thiadiazine by Indirect ELISA Test and Their Antimicrobial Activity

Malaria is a parasitic infection caused by a protozoon of the genus Plasmodium, transmitted to humans by female biting mosquitoes of the genus Anopheles. Chloroquine and its derivates have caused the parasite to develop drug resistance in endemic areas. For this reason, new anti-malarial drugs as treatments are crucial. This work aimed to evaluate the humoral response. with hyper-immune sera, of mice immunized with six derivatives of tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (bis-THTT) by indirect ELISA test. The cross-reactivity between the compounds as antigens and their microbial activity on Gram-positive and Gram-negative bacteria was evaluated. The results of the humoral evaluation by indirect ELISA show that three bis-THTTs react with almost all of the above. Besides, three compounds used as antigens stimulate the BALB/c mice’s immune system. The best combination of two antigens as a combined therapy displays similar absorbances between the antigens in the mixture, showing similar recognition by antibodies and their compounds. In addition, our results showed that different bis-THTT presented antimicrobial activity on Gram-positive bacteria, mainly on Staphylococcus aureus strains, and no inhibitory activity was observed on the Gram-negative bacteria tested

Catalytic Stereodivergent Synthesis of Steroid–Fulleropyrrolidine Hybrids

The diastereoselective synthesis of <i>cis</i> and <i>trans</i> steroid–fulleropyrrolidines hybrids by reaction of <i>N</i>-metalated azomethine ylides [Cu­(II) or Ag­(I)] with the appropriate chiral ligand and C₆₀ is described. The experimental findings reveal that the azomethine ylide stabilized by an allylic group cycloadds to [60]­fullerene in an efficient manner and with a good diastereomeric excess. Furthermore, the new generated stereocenters are fully controlled by the catalytic systems used without being influenced by the chirality of the steroid. Interestingly, by this synthetic methodology the each one of the four possible stereoisomers have efficiently been obtained and characterized by CD spectra