The effect of sinefungin on the macromolecular biosynthesis of Leishmania species

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Published: Jan 31, 2018
DOI: https://doi.org/10.12681/jhvms.15765
A. TZORA (Α. ΤΖΩΡΑ)
Department of Animal Production, Technological Educational Institution of Epirus
F. LAWRENCE
Institute de Chimie des Substances Naturelles, C.N.R.S., France
M. ROBERT-GERO
Institute de Chimie des Substances Naturelles, C.N.R.S., France
Abstract

The aim of the work presented here was the in vitro study of the action of the antibiotic sinefungin on the macromolecules DNA, RNA and the proteins of different isolates of Leismannia spp. in relation to the resistance or to the sensitivity of the strains examined. The mode of action of sinefungin of the Leishmania strains was detected by incorporating radiolabeled thymidine, uridine and leucine into promastigote forms, to study the synthesis of DNA, RNA and proteins respectively. In the sensitive strain L. tropica a statistically significant reduction of the rate of incorporation of thymidine to the DNA of the parasite, resulted to a 64% inhibition of leishmanial DNA synthesis by sinefungin at a concentration of 2.6 mM, when the time of action of the drug was 24 hours. In the sensitive strain L. tropica the reduction of the rate of incorporation of thymidine was depended on the concentration and the time of action of the drug. No inhibition of leishmanial RNA synthesis was observed. Our research showed that the action of the antibiotic sinefungin to the macromolecular biosynthesis of the protozoan Leishmania is independent of the strain and is strongly related with the expression of the sensitivity and the resistance of the strain. The main target of the antibiotic examined was the DNA of the Leishmania strains sensitive to the drug.

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References
Hamill R, Hoehn M. Α9145, a new adenine containing antifugal antibiotici. Discovery and isolation. J Antibiot 1973,26:463 - 465
Gordee RS, Butler TF. A9145, a new adenine containing antifugal antibiotic. II.Biological activity. J Antibiot 1973,26:466 – 470
Bachrach V, Schnur LF, El-On J, Greenblatt CL, Pearlman M, Robert-Gero M, Lederer E. Inhibitory activity of sinefungin and SIBA on the growth of promastigotes and amastigotes. FEBS Lett 1980,121:287 - 291
Fuller RW, Nagarajan R. Inhibition of methyltransferases by some new analogs of S-adenosylhomocysteine. Biochem Pharmacol 1978,27:1981 – 1983
Vedel M, Lawrence F, Robert-Gero M, Lederer E. The antifugal antibiotic sinefungin as a very active inhibitor of methyltransferases and of the transformation of chick embryo fibroblasts by Rous Sarcoma Virus. Res Commun 1978,85:371-376
Borchardt RT, Eideo LE, Wu 8, Rutiedge CO. Sinefungin a potent inhibitor of SAM-protein-O-methyltrasferases. Biochem Biophys Res Commun 1979,89:919 – 924
Paotantonacci P, Lawrence F, Robert-Gero M. Differential effect of sinefungin and its analogs on the multiplica5on of three leishmania species. Antimicrob Agents Chemother 1985,28:528-531
Τζώρα-Σκοΐίφου Α. Μελέτη του μηχανισμού δράσης του αντιβιοτικού σινεφουνγίνη στις προμαστιγωτές μορφές του παρασίτου λεϊσμάνια. Διδακτορική διατριβή. Πανεπιστήμιο Θεσσαλονίκης 1992.
Tzora-Skoufou A, Lawrence F, Robert-Gero M, Hadziandoniou M. Recherche de resistents spontanes a la sinefungine dans les souches de leishmanies provenant de Grece. Bulletin de la Société de Pasitologie 1990,8:1:19 – 24
Tzarnouranis N, Schnur LF, Gerifellou A, Pateraki E, Serie C. Leishmanissis in Greece. I .Isolation and identification of the parssite causing human and canine visceral leishmaniasis. Ann Trop Med and Parasite 1984,78:4:363 – 368
Frank C. Serologische Klassifizierung und biochemische indentifizierung von in Griecheland isolierten Leishmania- Stammen (Kinetoplastida: Trypanosomatidae). Dissertation- Universität Tubingen, 1991
Paolantonecci P, Lawrence F, Nolan LL, Robert Gero M, lohibition of leishmanial DNA synthesis by sinefungin. Biochem Pharmecol 1987,36:2813 – 2820
Χαντζηαντωνίου Μ. Μαζική καλλιέργεια της προμαστιγωτής μορφής του παρασίτου λεϊσμάνια-Παρασκευή νέου μονοφασικού υλικού. Διδακτορική διατριβή. Ιατρική Σχολή Πανεπιστημίου Αθηνών 1984.
Τσιρογιάννης Ε, Τσαγγάρης Θ. Ο κυτταρικός κύκλος και οι διαταραχε'ςτου. Γενική Παθολογική Ανατομική. Αφοί Κυριακίδη, Θεσσαλονίκη 1982, 47-49.
Glew RH, Saha AK, Das S, Remaley AT. Biochemistry of the leishmania species. Microbiological Reviews 1988,412-432
Schneider WC. Phosphorous compounds in animal tissues:extraction and estimation of deoxypentose nucleic acid and pentose nudeic acid. J Biol Chem 1945,161:293 – 303
Lowry QH, Rosebrough NL, Farr AL, Randall RJ. Protein measurment with the folin phenol reagent. J Biol Chem 1951,193:265 – 275
Tabachnick 8, Fidll L. Using multivariate Siatisticks. Harper and Row 1983, New York
Armitage P. Statistical Methods in Medical Research. Blackwell Scientific Publications 1973,Oxford
McCammon MT, Parks W. Inhibition of sterol transmethylation by S- adenosyl-homocysteine analogs. J Bacter 1981,145:106-112
Brun R, Krassner MS. Quantitave Ultrastructural Investigations of mitochondrial development in leishmania donovani during transformation. J Protozool 1976,23:493 – 497
Neal RA, Croff SL. An in vitro system for determining the activity of compounds against the intracellular amastigote form of Leishmania donovani. J Antimicrob Chemother 1984,14:463 – 475
Holmes AM, Cheriathyndam E, Kalinski A, Chang LMS. Isolation and Partial Characterization of DNA polymerase from Crithidia fasciculata. Mol Biochem Parasitol 1984,239:21-29
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