Trypanocidal and cell swelling activity of 20-deoxysalinomycin
(2022) In Experimental Parasitology 243.- Abstract
The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma brucei. Here, we report the evaluation of 20-deoxysalinomycin, a naturally occurring homolog to salinomycin, for trypanocidal and cell swelling activity. The concentration of 20-deoxysalinomycin required to reduce the growth rate of bloodstream-form trypanosomes by 50% was determined to be 0.12 μM and found to be 8 times more trypanocidal than that of salinomycin. Moreover, 20-deoxysalinomycin and salinomycin displayed similar cytotoxic activity against human HL-60 cells. Measured as the ratio of cytotoxic to trypanocidal activity, 20-deoxysalinomycin thus exhibits a... (More)
The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma brucei. Here, we report the evaluation of 20-deoxysalinomycin, a naturally occurring homolog to salinomycin, for trypanocidal and cell swelling activity. The concentration of 20-deoxysalinomycin required to reduce the growth rate of bloodstream-form trypanosomes by 50% was determined to be 0.12 μM and found to be 8 times more trypanocidal than that of salinomycin. Moreover, 20-deoxysalinomycin and salinomycin displayed similar cytotoxic activity against human HL-60 cells. Measured as the ratio of cytotoxic to trypanocidal activity, 20-deoxysalinomycin thus exhibits a four-fold higher selectivity compared to salinomycin. The stronger trypanocidal activity of 20-deoxysalinomycin is attributed to an enhanced ability to induce cell swelling in trypanosomes. The findings support 20-deoxysalinomycin as a useful lead in the rational development of new and improved anti-trypanosomal drugs.
(Less)
- author
- Steverding, Dietmar ; Strand, Daniel LU and Huczyński, Adam
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 20-Deoxysalinomycin, African trypanosomiasis, Polyether ionophores, Trypanosoma brucei
- in
- Experimental Parasitology
- volume
- 243
- article number
- 108414
- publisher
- Elsevier
- external identifiers
-
- pmid:36273616
- scopus:85140633972
- ISSN
- 0014-4894
- DOI
- 10.1016/j.exppara.2022.108414
- language
- English
- LU publication?
- yes
- id
- 25d6e3f2-0562-4f62-a7e6-18e3e14512c3
- date added to LUP
- 2022-12-06 12:37:12
- date last changed
- 2024-04-18 16:01:14
@article{25d6e3f2-0562-4f62-a7e6-18e3e14512c3,
abstract = {{<p>The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma brucei. Here, we report the evaluation of 20-deoxysalinomycin, a naturally occurring homolog to salinomycin, for trypanocidal and cell swelling activity. The concentration of 20-deoxysalinomycin required to reduce the growth rate of bloodstream-form trypanosomes by 50% was determined to be 0.12 μM and found to be 8 times more trypanocidal than that of salinomycin. Moreover, 20-deoxysalinomycin and salinomycin displayed similar cytotoxic activity against human HL-60 cells. Measured as the ratio of cytotoxic to trypanocidal activity, 20-deoxysalinomycin thus exhibits a four-fold higher selectivity compared to salinomycin. The stronger trypanocidal activity of 20-deoxysalinomycin is attributed to an enhanced ability to induce cell swelling in trypanosomes. The findings support 20-deoxysalinomycin as a useful lead in the rational development of new and improved anti-trypanosomal drugs.</p>}},
author = {{Steverding, Dietmar and Strand, Daniel and Huczyński, Adam}},
issn = {{0014-4894}},
keywords = {{20-Deoxysalinomycin; African trypanosomiasis; Polyether ionophores; Trypanosoma brucei}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Experimental Parasitology}},
title = {{Trypanocidal and cell swelling activity of 20-deoxysalinomycin}},
url = {{http://dx.doi.org/10.1016/j.exppara.2022.108414}},
doi = {{10.1016/j.exppara.2022.108414}},
volume = {{243}},
year = {{2022}},
}