Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets
2019
Аутори
Stevanović, StrahinjaSencanski, Milan
Danel, Mathieu
Menendez, Christophe
Belguedj, Roumaissa
Bouraiou, Abdelmalek
Nikolić, Katarina
Cojean, Sandrine
Loiseau, Philippe M.
Glisić, Sanja
Baltas, Michel
Garcia-Sosa, Alfonso T.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 mu M on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interes...ting molecular template for further development of new anti-leishmanial agents.
Кључне речи:
Leishmania / arginase / in silico / anti-target / in vitro / anti-leishmanial inhibitors / anti-targetИзвор:
Molecules, 2019, 24, 7Издавач:
- MDPI, Basel
Финансирање / пројекти:
DOI: 10.3390/molecules24071282
ISSN: 1420-3049
PubMed: 30986947
WoS: 000464948000008
Scopus: 2-s2.0-85063721713
Институција/група
PharmacyTY - JOUR AU - Stevanović, Strahinja AU - Sencanski, Milan AU - Danel, Mathieu AU - Menendez, Christophe AU - Belguedj, Roumaissa AU - Bouraiou, Abdelmalek AU - Nikolić, Katarina AU - Cojean, Sandrine AU - Loiseau, Philippe M. AU - Glisić, Sanja AU - Baltas, Michel AU - Garcia-Sosa, Alfonso T. PY - 2019 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3375 AB - Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 mu M on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents. PB - MDPI, Basel T2 - Molecules T1 - Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets VL - 24 IS - 7 DO - 10.3390/molecules24071282 ER -
@article{ author = "Stevanović, Strahinja and Sencanski, Milan and Danel, Mathieu and Menendez, Christophe and Belguedj, Roumaissa and Bouraiou, Abdelmalek and Nikolić, Katarina and Cojean, Sandrine and Loiseau, Philippe M. and Glisić, Sanja and Baltas, Michel and Garcia-Sosa, Alfonso T.", year = "2019", abstract = "Due to the lack of approved vaccines against human leishmaniasis and the limitations of the current chemotherapy inducing side effects and drug resistance, development of new, effective chemotherapeutic agents is essential. This study describes the synthesis of a series of novel oxadiazoles and indolizine-containing compounds. The compounds were screened in silico using an EIIP/AQVN filter followed by ligand-based virtual screening and molecular docking to parasite arginase. Top hits were further screened versus human arginase and finally against an anti-target battery to tag their possible interactions with proteins essential for the metabolism and clearance of many substances. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three compounds. One compound with an IC50 value of 2.18 mu M on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesting molecular template for further development of new anti-leishmanial agents.", publisher = "MDPI, Basel", journal = "Molecules", title = "Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets", volume = "24", number = "7", doi = "10.3390/molecules24071282" }
Stevanović, S., Sencanski, M., Danel, M., Menendez, C., Belguedj, R., Bouraiou, A., Nikolić, K., Cojean, S., Loiseau, P. M., Glisić, S., Baltas, M.,& Garcia-Sosa, A. T.. (2019). Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets. in Molecules MDPI, Basel., 24(7). https://doi.org/10.3390/molecules24071282
Stevanović S, Sencanski M, Danel M, Menendez C, Belguedj R, Bouraiou A, Nikolić K, Cojean S, Loiseau PM, Glisić S, Baltas M, Garcia-Sosa AT. Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets. in Molecules. 2019;24(7). doi:10.3390/molecules24071282 .
Stevanović, Strahinja, Sencanski, Milan, Danel, Mathieu, Menendez, Christophe, Belguedj, Roumaissa, Bouraiou, Abdelmalek, Nikolić, Katarina, Cojean, Sandrine, Loiseau, Philippe M., Glisić, Sanja, Baltas, Michel, Garcia-Sosa, Alfonso T., "Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets" in Molecules, 24, no. 7 (2019), https://doi.org/10.3390/molecules24071282 . .