| Title: |
Antiprotozoal activity of 6-aminonicotinamide against Leishmania infantum promastigotes |
| Authors: |
HANAU, Stefania; Almugadam, Shawgi; Dallocchio, Franco Pasquale Filippo; Contini, Carlo; Maritati, Martina; Longhi, Alessia; Rugna, Gianluca; Bellini, Tiziana |
| Contributors: |
Stefania Hanau, Shawgi Almugadam, Franco Dallocchio, Carlo Contini, Martina Maritati, Alessia Longhi, Gianluca Rugna, Tiziana Bellini; Hanau, Stefania; Almugadam, Shawgi; Dallocchio, Franco Pasquale Filippo; Contini, Carlo; Maritati, Martina; Longhi, Alessia; Rugna, Gianluca; Bellini, Tiziana |
| Publisher Information: |
ESCMID; CHE |
| Publication Year: |
2016 |
| Collection: |
Università degli Studi di Ferrara: CINECA IRIS |
| Subject Terms: |
leishmaniasis; 6-aminonicotinamide; chemoresistance |
| Description: |
Background Leishmaniasis (L) is one of the most important vector-borne human diseases, transmitted via infected female sandfly bite. Leishmania (L) protozoan parasites transmission is zoonotic, with dogs as main reservoir, but anthroponotic in the most hit Asia regions. In vertebrates L lives in macrophages. Diverse L species mainly cause visceral, cutaneous and mucocutaneous L,L. infantum visceral L in the Mediterranean region and in Latin America, (called there L. chagasi). Chemotherapy is fundamental since vaccines are available only for dogs, with limited efficacy. Drugs are lipid-associated amphotericin B, antimonials, pentamidine, paramomycin, miltefosine and few other compounds like ketoconazole for cutaneous L. Except for liposomal amphotericin B, combination therapy is recommended to avoid drug-resistance, as happened in India for antimonials, and to reduce side toxic effects presented by all these drugs. New compounds or drug repurposing are welcome. 6-aminonicotinamide (6AN) is an antimetabolite shown in some cell types to inhibit pentose phosphate pathway (PPP). It was initially proposed for cancer chemotherapy and psoriasis. Materials/methods L. infantum strain MO1 was cultured at 25 °C in RPMI containing 15% FBS and penicillin/streptomycin. 6AN (Sigma) solved in DMSO, aliquoted at -20°C, was diluted in RPMI as other compounds before use. Viable cells were counted by either hemocytometer or Alamar Blue fluorescence. For oxidative stress resistance evaluation, 6AN treated and control cells were diluted to 6 x 104 cells/mL and challenged 45 min with H2O2. Surviving parasites were counted using trypan blue and hemocytometer. 6AN treated and control cells were washed with PBS and lysed in 50 mM Tris, pH 7.5, 100 mM NaCl, 1% Triton X100, 5 mM EDTA and other protease inhibitors by freeze-thaw and sonication. 6-phosphogluconate dehydrogenase (6PGD) was assayed at 340 nm in presence of 6PG and NADP by microplate reader and normalized for the cells number. Treatments were in triplicate and in several ... |
| Document Type: |
conference object |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
ispartofbook:ESCMID eLibrary EV0804, 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Amsterdam 9-12 April 2016; 26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); firstpage:EV0804; lastpage:EV0804; numberofpages:1; serie:ESCMID eLibrary; https://hdl.handle.net/11392/2342919 |
| Availability: |
https://hdl.handle.net/11392/2342919 |
| Accession Number: |
edsbas.B06BBA0 |
| Database: |
BASE |