التفاصيل البيبلوغرافية
| العنوان: |
Well-Tolerated Amphotericin B Derivatives That Effectively Treat Visceral Leishmaniasis |
| المؤلفون: |
Christelle Morelle (3446330), Angana Mukherjee (183675), Jiabao Zhang (349829), Fereshteh Fani (11159999), Anuj Khandelwal (1923301), Hélène Gingras (11160002), Jocelyn Trottier (348489), Olivier Barbier (348493), Philippe Leprohon (133682), Martin D. Burke (1280013), Marc Ouellette (51263) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Sociology, Immunology, Cancer, Virology, Computational Biology, Chemical Sciences not elsewhere classified, Physical Sciences not elsewhere classified, AmB derivatives, female-specific liver toxicity, L . donovani, VL, Well-Tolerated Amphotericin B Deriv., Visceral Leishmaniasis Chemotherapy, line drug |
| الوصف: |
Chemotherapy against the neglected tropical disease visceral leishmaniasis (VL) is suboptimal with only four licensed drugs. Amphotericin B (AmB), despite its toxicity, remained a second line drug for a long time. However, the demonstration that liposomal AmB is highly effective against VL propelled it, despite its cost, to a first line drug in many countries. While several ongoing efforts are aiming at finding cheaper and stable AmB-formulations, an alternative strategy is the development of less-toxic AmB derivatives. We show here that two less-toxic AmB derivatives with the carboxylate at position 16 of AmB derivatized to a methyl urea (AmB-MU) or amino urea (AmB-AU) are active in vitro against Leishmania donovani , both as free-living parasites as well as their intracellular form. Both less-toxic derivatives, similarly to AmB, target the ergosterol pathway of L. donovani . While the AmB-AU derivative showed female-specific liver toxicity in vivo, the AmB-MU derivative was well-tolerated and more effective than AmB against experimental VL. These studies are an important step for improving AmB-based therapy against a prevalent parasitic disease. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Well-Tolerated_Amphotericin_B_Derivatives_That_Effectively_Treat_Visceral_Leishmaniasis/15023087Test |
| DOI: |
10.1021/acsinfecdis.1c00245.s001 |
| الإتاحة: |
https://doi.org/10.1021/acsinfecdis.1c00245.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.C0E04EC4 |
| قاعدة البيانات: |
BASE |
