Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms
Visceral leishmaniasis, the most severe form of the disease, is caused by L. donovani and L. infantum parasites; cutaneous leishmaniasis is the most common endemic form of leishmaniasis and mainly caused by L. tropica and L. major. We have previously described a series of thiazolopyrimidine derivati...
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Elsevier
2024-12-01
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| Series: | European Journal of Medicinal Chemistry Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417424001006 |
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| author | Gulsah Bayraktar Pascal Marchand Euzébio Guimarães Barbosa Marilia Cecilia da Silva Karen Cacilda Weber Sandrine Cojean Merve Saylam Huseyin Istanbullu |
| author_facet | Gulsah Bayraktar Pascal Marchand Euzébio Guimarães Barbosa Marilia Cecilia da Silva Karen Cacilda Weber Sandrine Cojean Merve Saylam Huseyin Istanbullu |
| author_sort | Gulsah Bayraktar |
| collection | DOAJ |
| description | Visceral leishmaniasis, the most severe form of the disease, is caused by L. donovani and L. infantum parasites; cutaneous leishmaniasis is the most common endemic form of leishmaniasis and mainly caused by L. tropica and L. major. We have previously described a series of thiazolopyrimidine derivatives and reported their antipromastigote activities against various parasites. In this study, we also investigated their activities against L. donovani and L. major axenic amastigotes, intramacrophage amastigotes and cytotoxicity on macrophages to assess selectivity. As a result, five of the compounds tested showed no cytotoxicity on the macrophage cell line; their anti-amastigote activity was close to the positive control, miltefosine. These results confirm the antileishmanial activity of the thiazolopyrimidine scaffold and demonstrate that this may be a starting point for the generation of new lead compounds for treating visceral leishmaniasis and cutaneous leishmaniasis. To elucidate the mechanism of action, we also performed several ligand- and structure-based in silico studies. |
| format | Article |
| id | doaj-art-8e965adc4bc04a8090f2e5322b45b8f1 |
| institution | Kabale University |
| issn | 2772-4174 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj-art-8e965adc4bc04a8090f2e5322b45b8f12024-12-05T05:21:59ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742024-12-0112100228Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote formsGulsah Bayraktar0Pascal Marchand1Euzébio Guimarães Barbosa2Marilia Cecilia da Silva3Karen Cacilda Weber4Sandrine Cojean5Merve Saylam6Huseyin Istanbullu7Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, Bornova, 35100, Izmir, TurkeyNantes Université, Cibles et médicaments des infections et de l'immunité, IICiMed, UR 1155, F-44000 Nantes, FranceDepartment of Pharmacy, Federal University of Rio Grande do Norte University Campus I, CEP 59012-570, Natal, RN, BrazilDepartment of Chemistry, Federal University of Paraiba, CEP 58051-900, João Pessoa, PB, BrazilDepartment of Chemistry, Federal University of Paraiba, CEP 58051-900, João Pessoa, PB, BrazilUMR BIPAR, Laboratory of Animal Health, Anses, INRAe, EnvA, F-94700, Maisons-Alfort, France; BioCIS Biomolécules: conception, Isolement, synthèse, chimiothérapie antiparasitaire, Université Paris-Saclay, F-91400, Orsay, FranceDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Izmir Katip Celebi University, Cigli, 35620, Izmir, TurkeyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Izmir Katip Celebi University, Cigli, 35620, Izmir, Turkey; Corresponding author. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Izmir Katip Celebi University, Cigli, 35620, Izmir, Turkey.Visceral leishmaniasis, the most severe form of the disease, is caused by L. donovani and L. infantum parasites; cutaneous leishmaniasis is the most common endemic form of leishmaniasis and mainly caused by L. tropica and L. major. We have previously described a series of thiazolopyrimidine derivatives and reported their antipromastigote activities against various parasites. In this study, we also investigated their activities against L. donovani and L. major axenic amastigotes, intramacrophage amastigotes and cytotoxicity on macrophages to assess selectivity. As a result, five of the compounds tested showed no cytotoxicity on the macrophage cell line; their anti-amastigote activity was close to the positive control, miltefosine. These results confirm the antileishmanial activity of the thiazolopyrimidine scaffold and demonstrate that this may be a starting point for the generation of new lead compounds for treating visceral leishmaniasis and cutaneous leishmaniasis. To elucidate the mechanism of action, we also performed several ligand- and structure-based in silico studies.http://www.sciencedirect.com/science/article/pii/S2772417424001006AntileishmanialAxenic amastigoteIntramacrophage amastigoteThiazolopyrimidineIn silico studies |
| spellingShingle | Gulsah Bayraktar Pascal Marchand Euzébio Guimarães Barbosa Marilia Cecilia da Silva Karen Cacilda Weber Sandrine Cojean Merve Saylam Huseyin Istanbullu Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms European Journal of Medicinal Chemistry Reports Antileishmanial Axenic amastigote Intramacrophage amastigote Thiazolopyrimidine In silico studies |
| title | Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms |
| title_full | Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms |
| title_fullStr | Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms |
| title_full_unstemmed | Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms |
| title_short | Biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous Leishmania spp. amastigote forms |
| title_sort | biological properties and in silico studies of thiazolopyrimidine derivatives active against visceral and cutaneous leishmania spp amastigote forms |
| topic | Antileishmanial Axenic amastigote Intramacrophage amastigote Thiazolopyrimidine In silico studies |
| url | http://www.sciencedirect.com/science/article/pii/S2772417424001006 |
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