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Christophe Brugidou - One of the best experts on this subject based on the ideXlab platform.
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optimized transitory ectopic expression of promastigote surface Antigen protein in nicotiana benthamiana a potential Anti Leishmaniasis vaccine candidate
Journal of Bioscience and Bioengineering, 2018Co-Authors: Severine Lacombe, Martine Bangratz, Jeanpaul Brizard, Elodie Petitdidier, Julie Pagniez, Drissa Sereme, Jeanloup Lemesre, Christophe BrugidouAbstract: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 Anti-Leishmaniasis 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 - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 5 spirocyclohexyl 2 4 dithiohydantoin derivatives a potential Anti Leishmaniasis agent
Monatshefte Fur Chemie, 2009Co-Authors: Abdelsattar Hamad S Elgazwy, Saad R Attaallah, Sherif M. A. S. KeshkAbstract: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].
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Synthesis of 5-spirocyclohexyl-2,4-dithiohydantoin derivatives: a potential Anti-Leishmaniasis agent
Monatshefte für Chemie - Chemical Monthly, 2008Co-Authors: Abdel-sattar S. Hamad Elgazwy, Saad R. Atta-allha, Sherif M. A. S. KeshkAbstract: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 - One of the best experts on this subject based on the ideXlab platform.
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optimized transitory ectopic expression of promastigote surface Antigen protein in nicotiana benthamiana a potential Anti Leishmaniasis vaccine candidate
Journal of Bioscience and Bioengineering, 2018Co-Authors: Severine Lacombe, Martine Bangratz, Jeanpaul Brizard, Elodie Petitdidier, Julie Pagniez, Drissa Sereme, Jeanloup Lemesre, Christophe BrugidouAbstract: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 Anti-Leishmaniasis 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.
Mastewal Misganaw - One of the best experts on this subject based on the ideXlab platform.
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treatment patterns and effectivness of Anti Leishmaniasis agents for patients with cutaneous Leishmaniasis at boru meda hospital south wollo north east ethiopia 2017 18
Journal of clinical & experimental dermatology research, 2018Co-Authors: Tsehai Seife, Ayikel Kassa Benecha, Feleke Tilahun Zewdu, Alie Ayal, Mastewal MisganawAbstract:Background: Cutaneous Leishmaniasis (CL) is one of the endemic and neglected diseases known to exist in Ethiopian highlands. However, a neglected tropical disease overshadowed by lack of effective Anti-Leishmaniasis agent in Ethiopia. Thus, high number of population is faced for various degree of socio-economical and psychosocial morbidity. Hence, this study was initiated and conducted from July-February, 2017/18 to assess the patterns and effectiveness of different types of Anti-Leishmaniasis agents in Boru Meda Hospital, Dessie District. Methods: A cohort study design was employed in six treatment categories via randomly allocated cutaneouse patients from three clinical types at Boru Meda hospital Dermatology department. Detailed clinical assessment, biopsy/FNAC, and skin slit smear leishmania parasite detection were done to confirm clinical suspension. Then, the intended treatment types were administered for three cycle. Finally the data were analyzed using Epi-info, SPSS and the results presented using graphs and tables. Results: Among patients with mucocutaneouse Leishmaniasis who have took systemic SSG with IL SSG 85.7%, systemic SSG with Allopurinol was as effective as 78.6%. Patients with DCL who took both systemic SSG with Allopurinol 80% and systemic SSG and local therapy both cryotherapy and IL SSG had a clinical cure rate of 85.7%. In addition, patients who diagnosed as localized cutaneouse Leishmaniasis and took only cryotherapy 92.3% where as those patients who had a combined local therapy of both cryotherapy and IL SSG therapy showed clinical cure rate of 96.1%. Conclusion: As our study showed for any clinical type of cutaneouse Leishmaniasis, administering combined forms (Pentavalent Antimonial with local therapies i.e cryotherapy or/and IL SSG ) of Anti-Leishmaniasis agents had a better cure rate than single therapies.
O V Sizova - One of the best experts on this subject based on the ideXlab platform.
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Synthetic neoglycoconjugates of cell-surface phosphoglycans of Leishmania as potential Anti-parasite carbohydrate vaccines
Biochemistry (Moscow), 2011Co-Authors: Andrei V Nikolaev, O V SizovaAbstract:Leishmania are a genus of sandfly-transmitted protozoan parasites that cause a spectrum of debilitating and often fatal diseases in humans throughout the tropics and subtropics. During the parasite life cycle, Leishmania survive and proliferate in highly hostile environments. Their survival strategies involve the formation of an elaborate and dense cell-surface glycocalyx composed of diverse stage-specific glycoconjugates that form a protective barrier. Phosphoglycans constitute the variable structural and functional domain of major cell-surface lipophosphoglycan and secreted proteophosphoglycans. In this paper, we discuss structural aspects of various phosphoglycans from Leishmania with the major emphasis on the chemical preparation of neoglycoconjugates (neoglycoproteins and neoglycolipids) based on Leishmania lipophosphoglycan structures as well as the immunological evaluation for some of them as potential Anti-Leishmaniasis vaccines.
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synthetic glycoconjugates based on leishmania lipophosphoglycan structures as potential Anti Leishmaniasis vaccines
2010Co-Authors: Andrei V Nikolaev, Nawaf Almaharik, O V SizovaAbstract:Leishmania are a genus of sandfly-transmitted protozoan parasites that cause a spectrum of debilitating and often fatal diseases in humans throughout the tropics and subtropics. The disease (termed Leishmaniasis) torments over 12 million people worldwide, making 2.4 million people disabled and causi...
