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Anti Leishmaniasis

The Experts below are selected from a list of 153 Experts worldwide ranked by ideXlab platform

Christophe Brugidou – 1st expert on this subject based on the ideXlab platform

  • optimized transitory ectopic expression of promastigote surface Antigen protein in nicotiana benthamiana a potential Anti Leishmaniasis vaccine candidate
    Journal of Bioscience and Bioengineering, 2018
    Co-Authors: Severine Lacombe, Martine Bangratz, Jeanpaul Brizard, Elodie Petitdidier, Julie Pagniez, Drissa Sereme, Jeanloup Lemesre, Christophe Brugidou

    Abstract:

    In recent years, plants have been shown to be an efficient alternative expression system for high-value pharmaceuticals such as vaccines. However, constitutive expression of recombinant protein remains uncertain on their level of production and biological activity. To overcome these problems, transitory expression systems have been developed. Here, a series of experiments were performed to determine the most effective conditions to enhance vaccine Antigen transient accumulation in Nicotiana benthamiana leaves using the promastigote surface Antigen (PSA) from the parasitic protozoan Leishmania infantum. This protein has been previously identified as the major Antigen of a licensed canine AntiLeishmaniasis vaccine. The classical prokaryote Escherichia coli biosystem failed in accumulating PSA. Consequently, the standard plant system based on N. benthamiana has been optimized for the production of putatively active PSA. First, the RNA silencing defense mechanism set up by the plant against PSA ectopic expression was abolished by using three viral suppressors acting at different steps of the RNA silencing pathway. Then, we demonstrated that the signal peptide at the N-terminal side of the PSA is required for its accumulation. The PSA ER signaling and retention with the PSA signal peptide and the KDEL motif, respectively were optimized to significantly increase its accumulation. Finally, we demonstrate that the production of recombinant PSA in N. benthamiana leaves allows the conservation of its immunogenic property. These approaches demonstrate that based on these optimizations, plant based systems can be used to effectively produce the biological active PSA protein.

Sherif M. A. S. Keshk – 2nd expert on this subject based on the ideXlab platform

  • synthesis of 5 spirocyclohexyl 2 4 dithiohydantoin derivatives a potential Anti Leishmaniasis agent
    Monatshefte Fur Chemie, 2009
    Co-Authors: Abdelsattar Hamad S Elgazwy, Saad R Attaallah, Sherif M. A. S. Keshk

    Abstract:

    Abstract A series of spiro-dithiohydantoins were syn-thesized by heating a mixture of 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt and 3-chloropropanoylchloride. These compounds were synthesized and evalu-ated for their activity against five Leishmanial strains in thepromastigote stage in vitro. Seventy-two hours inoculationof a variety of products gave an IC 100 and average IC 50 values of 1.25 and 0.376 mg/cm 3 against all Leishmanialstrains tested.Keywords Dithiohydantoins Spiro-dithiohydantoins 1,3-Diazaspiro[4,5] decane-2,4-dithione LeishmaniasisIntroductionIn connection with our previous research work related toaza-spiro compounds, such as 5-spirocyclohexyl-2,4-dith-iohydantoin [1–7], spiro-thiopyrano[2,3-d]thiazolidines [8]andisothiazoles[9],weaimedatthesynthesisofcompoundswith Anti-leishmania activity based on the spiro-dithiohyd-antoin scaffold. It seemed of interest to us to prepare new5-spirocyclohexyl-2,4-dithiohydantoin derivatives bearingsome resemblance to the known drugs 5-ethyl-5-phen-ylhydantoin (Nirvanol) [10–12] and 5,5-diphenylhydantoin(DilAntin) [13]. Small heterocyclic molecules are one of thepredominant types of building block in medicinal chemistry[14, 15], and among the ‘‘drug-like’’ heterocycles, dith-iohydantoins have been widely used for constructingproducts with pharmaceutical applications [16]. Dith-iohydantoins are sulfur analogs of hydantoins with bothcarbonyl groups replaced by thiocarbonyl groups. Amongthe known dithiohydantoins, 2-thiohydantoins are mostnotably known due to their wide applications as hypolipi-demic, Anticarcinogenic, Antimutagenic, Antithyroidal, andAntiviral agents [17].We now report a simple method for the preparation of5-spiro-cyclohexyl-2,4-dithiohydantoin derivatives that caneasily be scaled up in the laboratory. The reaction of5-spirocyclohexyl-2,4-dithionhydantoin (1) with 1- or2-mole equivalents of 3-chloropropanoyl chloride wasexamined, and the synthesized compounds were testedagainst five Leishmanial strains. In continuation [18, 19]ofour efforts toward the synthesis of heterocyclic compounds,an efficient and practical preparation of 5-spirocyclohexy-2,4-dithiohydantoin derivatives 1–9 is shown.Results and discussionSynthesisThe direct condensation between 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt 2 and 3-chloropropanoylchloride produces 5-spirocyclohexyl-2,4-dithiohydantoinderivatives 3–9 in moderate to high yields (Scheme 1).Spirocyclohexyl-2,4-dithiohydantoin (1) was synthesizedin high yield (96%) [1–5, 20]. The 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt (2) was readily obtained bystirring 1 with ice-cooled KOH solution in ethanol [21, 22].

  • Synthesis of 5-spirocyclohexyl-2,4-dithiohydantoin derivatives: a potential AntiLeishmaniasis agent
    Monatshefte für Chemie – Chemical Monthly, 2008
    Co-Authors: Abdel-sattar S. Hamad Elgazwy, Saad R. Atta-allha, Sherif M. A. S. Keshk

    Abstract:

    A series of spiro-dithiohydantoins were synthesized by heating a mixture of 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt and 3-chloropropanoyl chloride. These compounds were synthesized and evaluated for their activity against five Leishmanial strains in the promastigote stage in vitro. Seventy-two hours inoculation of a variety of products gave an IC _ 100 and average IC _50 values of 1.25 and 0.376 mg/cm^3 against all Leishmanial strains tested. Graphical Abstract

Severine Lacombe – 3rd expert on this subject based on the ideXlab platform

  • optimized transitory ectopic expression of promastigote surface Antigen protein in nicotiana benthamiana a potential Anti Leishmaniasis vaccine candidate
    Journal of Bioscience and Bioengineering, 2018
    Co-Authors: Severine Lacombe, Martine Bangratz, Jeanpaul Brizard, Elodie Petitdidier, Julie Pagniez, Drissa Sereme, Jeanloup Lemesre, Christophe Brugidou

    Abstract:

    In recent years, plants have been shown to be an efficient alternative expression system for high-value pharmaceuticals such as vaccines. However, constitutive expression of recombinant protein remains uncertain on their level of production and biological activity. To overcome these problems, transitory expression systems have been developed. Here, a series of experiments were performed to determine the most effective conditions to enhance vaccine Antigen transient accumulation in Nicotiana benthamiana leaves using the promastigote surface Antigen (PSA) from the parasitic protozoan Leishmania infantum. This protein has been previously identified as the major Antigen of a licensed canine AntiLeishmaniasis vaccine. The classical prokaryote Escherichia coli biosystem failed in accumulating PSA. Consequently, the standard plant system based on N. benthamiana has been optimized for the production of putatively active PSA. First, the RNA silencing defense mechanism set up by the plant against PSA ectopic expression was abolished by using three viral suppressors acting at different steps of the RNA silencing pathway. Then, we demonstrated that the signal peptide at the N-terminal side of the PSA is required for its accumulation. The PSA ER signaling and retention with the PSA signal peptide and the KDEL motif, respectively were optimized to significantly increase its accumulation. Finally, we demonstrate that the production of recombinant PSA in N. benthamiana leaves allows the conservation of its immunogenic property. These approaches demonstrate that based on these optimizations, plant based systems can be used to effectively produce the biological active PSA protein.