Synthesis, In Silico, and In Vitro Evaluation of Anti-Leishmanial Activity of Oxadiazoles and Indolizine Containing Compounds Flagged against Anti-Targets
Authors
Stevanović, Strahinja
Senćanski, Milan V.

Danel, Mathieu
Menendez, Christophe
Belguedj, Roumaissa
Bouraiou, Abdelmalek
Nikolić, Katarina M.

Cojean, Sandrine
Loiseau, Philippe Marie
Glišić, Sanja

Baltas, Michel
García-Sosa, Alfonso T.

Article (Published version)
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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 µM on Leishmania donovani intramacrophage amastigotes is clearly better positioned than the others as an interesti...ng molecular template for further development of new anti-leishmanial agents.
Keywords:
Leishmania / arginase / in silico / anti-target / in vitro / anti-leishmanial inhibitors / anti-targetSource:
Molecules, 2019, 24, 7, 1282-Funding / projects:
- Application of the EIIP/ISM bioinformatics platform in discovery of novel therapeutic targets and potential therapeutic molecules (RS-173001)
- Haridus-ja Teadusministeerium [Grant IUT34-14]
Note:
- This article belongs to the Special Issue COST CM1307: Targeted Chemotherapy towards Diseases Caused by Endoparasites—Proceedings in Medicinal and Natural Product Chemistry
DOI: 10.3390/molecules24071282
ISSN: 1420-3049
PubMed: 30986947
WoS: 000464948000008
Scopus: 2-s2.0-85063721713
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VinčaTY - JOUR AU - Stevanović, Strahinja AU - Senćanski, Milan V. AU - Danel, Mathieu AU - Menendez, Christophe AU - Belguedj, Roumaissa AU - Bouraiou, Abdelmalek AU - Nikolić, Katarina M. AU - Cojean, Sandrine AU - Loiseau, Philippe Marie AU - Glišić, Sanja AU - Baltas, Michel AU - García-Sosa, Alfonso T. PY - 2019 UR - https://www.mdpi.com/1420-3049/24/7/1282 UR - https://vinar.vin.bg.ac.rs/handle/123456789/8137 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 µM 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. 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 SP - 1282 DO - 10.3390/molecules24071282 ER -
@article{ author = "Stevanović, Strahinja and Senćanski, Milan V. and Danel, Mathieu and Menendez, Christophe and Belguedj, Roumaissa and Bouraiou, Abdelmalek and Nikolić, Katarina M. and Cojean, Sandrine and Loiseau, Philippe Marie and Glišić, Sanja and Baltas, Michel and García-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 µM 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.", 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", pages = "1282", doi = "10.3390/molecules24071282" }
Stevanović, S., Senćanski, M. V., Danel, M., Menendez, C., Belguedj, R., Bouraiou, A., Nikolić, K. M., Cojean, S., Loiseau, P. M., Glišić, S., Baltas, M.,& García-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, 24(7), 1282. https://doi.org/10.3390/molecules24071282
Stevanović S, Senćanski MV, Danel M, Menendez C, Belguedj R, Bouraiou A, Nikolić KM, Cojean S, Loiseau PM, Glišić S, Baltas M, García-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):1282. doi:10.3390/molecules24071282 .
Stevanović, Strahinja, Senćanski, Milan V., Danel, Mathieu, Menendez, Christophe, Belguedj, Roumaissa, Bouraiou, Abdelmalek, Nikolić, Katarina M., Cojean, Sandrine, Loiseau, Philippe Marie, Glišić, Sanja, Baltas, Michel, García-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):1282, https://doi.org/10.3390/molecules24071282 . .