Novel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulations
Pathogenic <i>Acanthamoeba</i> produce keratitis and fatal granulomatous amoebic encephalitis. Treatment remains problematic and often ineffective, suggesting the need for the discovery of novel compounds. For the first time, here we evaluated the effects of the anticancer drugs Irosusta...
| Prif Awduron: | , , , , , , , , , , |
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| Fformat: | Journal article |
| Iaith: | English |
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MDPI
2023
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| _version_ | 1826310205806215168 |
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| author | Siddiqui, R Rawas-Qalaji, M El-Gamal, MI Sajeev, S Jagal, J Zaraei, S-O Sbenati, RM Anbar, HS Dohle, W Potter, BVL Khan, NA |
| author_facet | Siddiqui, R Rawas-Qalaji, M El-Gamal, MI Sajeev, S Jagal, J Zaraei, S-O Sbenati, RM Anbar, HS Dohle, W Potter, BVL Khan, NA |
| author_sort | Siddiqui, R |
| collection | OXFORD |
| description | Pathogenic <i>Acanthamoeba</i> produce keratitis and fatal granulomatous amoebic encephalitis. Treatment remains problematic and often ineffective, suggesting the need for the discovery of novel compounds. For the first time, here we evaluated the effects of the anticancer drugs Irosustat and STX140 alone, as well as their nanoformulations, against <i>A. castellanii</i> via amoebicidal, excystment, cytopathogenicity, and cytotoxicity assays. Nanoformulations of the compounds were successfully synthesized with high encapsulation efficiency of 94% and 82% for Irosustat and STX140, respectively. Nanoparticles formed were spherical in shape and had a unimodal narrow particle size distribution, mean of 145 and 244 nm with a polydispersity index of 0.3, and surface charge of −14 and −15 mV, respectively. Irosustat and STX140 exhibited a biphasic release profile with almost 100% drug released after 48 h. Notably, Irosustat significantly inhibited <i>A. castellanii</i> viability and amoebae-mediated cytopathogenicity and inhibited the phenotypic transformation of amoebae cysts into the trophozoite form, however their nanoformulations depicted limited effects against amoebae but exhibited minimal cytotoxicity when tested against human cells using lactate dehydrogenase release assays. Accordingly, both compounds have potential for further studies, with the hope of discovering novel anti-<i>Acanthamoeba</i> compounds, and potentially developing targeted therapy against infections of the central nervous system. |
| first_indexed | 2024-03-07T07:48:38Z |
| format | Journal article |
| id | oxford-uuid:88935b2b-18ba-4ec3-8679-659c9677375a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:48:38Z |
| publishDate | 2023 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oxford-uuid:88935b2b-18ba-4ec3-8679-659c9677375a2023-06-29T12:11:34ZNovel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulationsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:88935b2b-18ba-4ec3-8679-659c9677375aEnglishSymplectic ElementsMDPI2023Siddiqui, RRawas-Qalaji, MEl-Gamal, MISajeev, SJagal, JZaraei, S-OSbenati, RMAnbar, HSDohle, WPotter, BVLKhan, NAPathogenic <i>Acanthamoeba</i> produce keratitis and fatal granulomatous amoebic encephalitis. Treatment remains problematic and often ineffective, suggesting the need for the discovery of novel compounds. For the first time, here we evaluated the effects of the anticancer drugs Irosustat and STX140 alone, as well as their nanoformulations, against <i>A. castellanii</i> via amoebicidal, excystment, cytopathogenicity, and cytotoxicity assays. Nanoformulations of the compounds were successfully synthesized with high encapsulation efficiency of 94% and 82% for Irosustat and STX140, respectively. Nanoparticles formed were spherical in shape and had a unimodal narrow particle size distribution, mean of 145 and 244 nm with a polydispersity index of 0.3, and surface charge of −14 and −15 mV, respectively. Irosustat and STX140 exhibited a biphasic release profile with almost 100% drug released after 48 h. Notably, Irosustat significantly inhibited <i>A. castellanii</i> viability and amoebae-mediated cytopathogenicity and inhibited the phenotypic transformation of amoebae cysts into the trophozoite form, however their nanoformulations depicted limited effects against amoebae but exhibited minimal cytotoxicity when tested against human cells using lactate dehydrogenase release assays. Accordingly, both compounds have potential for further studies, with the hope of discovering novel anti-<i>Acanthamoeba</i> compounds, and potentially developing targeted therapy against infections of the central nervous system. |
| spellingShingle | Siddiqui, R Rawas-Qalaji, M El-Gamal, MI Sajeev, S Jagal, J Zaraei, S-O Sbenati, RM Anbar, HS Dohle, W Potter, BVL Khan, NA Novel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulations |
| title | Novel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulations |
| title_full | Novel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulations |
| title_fullStr | Novel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulations |
| title_full_unstemmed | Novel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulations |
| title_short | Novel anti-Acanthamoebic activities of Irosustat and STX140 and their nanoformulations |
| title_sort | novel anti acanthamoebic activities of irosustat and stx140 and their nanoformulations |
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