title: Cell death features induced in Leishmania major by 1,3,4-thiadiazole derivatives.
abstract: Under a variety of stress conditions, Leishmania species display some morphological and biochemical features characteristic of mammalian programmed cell death or necrosis. Nitroheteroaryl-1,3,4-thiadiazoles induce cell death in Leishmania major (L. major). Putative mechanisms of action of these compounds were investigated in vitro at cellular and molecular levels. We used colorimetric assay to measure acid phosphatase activity which is an indicator of cell viability in the promastigotes. The mode of toxicity was determined by detection of phosphatidylserine translocation to the surface, evaluation of cell membrane integrity, and in situ dUTP nick end-labeling assay. We also determined poly-ADP-ribose polymerase-like protein (PARP) level in the parasites after treatment. A significant reduction of acid phosphatase level, one of the most crucial and virulent factors of the parasite was found in parasites treated with 1,3,4-thiadiazole derivatives. In addition, 1,3,4-thiadiazole derivatives induced loss of plasma membrane integrity, DNA breakage, proteolysis of PARP and necrotic-like death in the parasites.
authors.affiliation: Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran. ardestani@ibb.ut.ac.ir
authors.forename: Sussan K
authors.initials: SK
authors.lastname: Ardestani
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Poorrajab
authors.forename: Sepideh
authors.initials: S
authors.lastname: Razmi
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Soheila
authors.initials: S
authors.lastname: Ajdary
authors.forename: Behnaz
authors.initials: B
authors.lastname: Gharegozlou
authors.forename: Mina
authors.initials: M
authors.lastname: Behrouzi-Fardmoghadam
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis / Q000187:drug effects; D017304:Annexin A5; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000031:analogs & derivatives; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D020128:Inhibitory Concentration 50; D018320:Leishmania major / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; D003609:Dactinomycin; C025942:7-aminoactinomycin D; D011065:Poly(ADP-ribose) Polymerases; D000135:Acid Phosphatase