Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>)
Leishmaniasis is affirmed as a category one disease (most emerging and unmanageable) by the World Health Organization (WHO), affecting 98 countries with an annual global incidence of ~1.2 million cases. Options for chemotherapeutic treatment are limited due to drug resistance and cytotoxicity. Thus,...
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MDPI AG
2022-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/8/1005 |
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| author | Sayyed Ibrahim Shah Fazli Nasir Nadia Shamshad Malik Muhammad Alamzeb Muhammad Abbas Inayat Ur Rehman Fazli Khuda Yasir Shah Khang Weh Goh Alam Zeb Long Chiau Ming |
| author_facet | Sayyed Ibrahim Shah Fazli Nasir Nadia Shamshad Malik Muhammad Alamzeb Muhammad Abbas Inayat Ur Rehman Fazli Khuda Yasir Shah Khang Weh Goh Alam Zeb Long Chiau Ming |
| author_sort | Sayyed Ibrahim Shah |
| collection | DOAJ |
| description | Leishmaniasis is affirmed as a category one disease (most emerging and unmanageable) by the World Health Organization (WHO), affecting 98 countries with an annual global incidence of ~1.2 million cases. Options for chemotherapeutic treatment are limited due to drug resistance and cytotoxicity. Thus, the search for new chemical compounds is instantly desirable. In this study, we used two compounds, i.e., 10-hydroxy chondrofoline and tafenoquine, for their antileishmanial activity against <i>L. tropica</i> (HTD<sub>7</sub>). First, the cytotoxicity assay of the test compounds against THP-1 cells was carried out, and these compounds were found safe. Intra-THP-1 amastigote activity (<i>in vitro</i>) was performed, which was then followed by the <i>in vivo</i> activity of 10-hydroxy chondrofoline in the murine cutaneous leishmaniasis (CL) model. A total of three concentrations were used, i.e., 25, 50, and 100 µM, to check the <i>in vitro</i> activity of the test compounds against the amastigotes. 10-hydroxy chondrofoline was found to be the most potent compound <i>in vitro</i> (and thus was selected for <i>in vivo</i> studies) with an LD<sub>50</sub> value of 43.80 µM after 48 h incubation, whilst tafenoquine had an LD<sub>50</sub> value of 53.57 µM. <i>In vivo</i> activity was conducted by injecting 10-hydroxy chondrofoline in the left hind foot of the infected BALB/c mice, where it caused a statistically significant 58.3% (F = 14.18; <i>p</i> = 0.002) reduction in lesion size (0.70 ± 0.03 mm) when compared with negative control (1.2 ± 0.3 mm). |
| first_indexed | 2024-03-09T03:58:40Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T03:58:40Z |
| publishDate | 2022-08-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-954c8faec4ae4eaba9af2f7cff48f94b2023-12-03T14:16:31ZengMDPI AGPharmaceuticals1424-82472022-08-01158100510.3390/ph15081005Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>)Sayyed Ibrahim Shah0Fazli Nasir1Nadia Shamshad Malik2Muhammad Alamzeb3Muhammad Abbas4Inayat Ur Rehman5Fazli Khuda6Yasir Shah7Khang Weh Goh8Alam Zeb9Long Chiau Ming10Department of Pharmacy, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, PakistanDepartment of Pharmacy, University of Peshawar, Khyber Pakhtunkhwa 25100, PakistanFaculty of Pharmacy, Capital University of Science and Technology, Islamabad 44000, PakistanDepartment of Chemistry, University of Kotli, Kotli 11100, PakistanDepartment of Pharmacy, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, PakistanDepartment of Pharmacy, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, PakistanDepartment of Pharmacy, University of Peshawar, Khyber Pakhtunkhwa 25100, PakistanDepartment of Pharmacy, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, PakistanFaculty of Data Science and Information Technology, INTI International University, Nilai 71800, MalaysiaDepartment of Biochemistry, University of Malakand, Khyber Pakhtunkhwa 18800, PakistanPAP Rashidah Sa’adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Gadong BE1410, BruneiLeishmaniasis is affirmed as a category one disease (most emerging and unmanageable) by the World Health Organization (WHO), affecting 98 countries with an annual global incidence of ~1.2 million cases. Options for chemotherapeutic treatment are limited due to drug resistance and cytotoxicity. Thus, the search for new chemical compounds is instantly desirable. In this study, we used two compounds, i.e., 10-hydroxy chondrofoline and tafenoquine, for their antileishmanial activity against <i>L. tropica</i> (HTD<sub>7</sub>). First, the cytotoxicity assay of the test compounds against THP-1 cells was carried out, and these compounds were found safe. Intra-THP-1 amastigote activity (<i>in vitro</i>) was performed, which was then followed by the <i>in vivo</i> activity of 10-hydroxy chondrofoline in the murine cutaneous leishmaniasis (CL) model. A total of three concentrations were used, i.e., 25, 50, and 100 µM, to check the <i>in vitro</i> activity of the test compounds against the amastigotes. 10-hydroxy chondrofoline was found to be the most potent compound <i>in vitro</i> (and thus was selected for <i>in vivo</i> studies) with an LD<sub>50</sub> value of 43.80 µM after 48 h incubation, whilst tafenoquine had an LD<sub>50</sub> value of 53.57 µM. <i>In vivo</i> activity was conducted by injecting 10-hydroxy chondrofoline in the left hind foot of the infected BALB/c mice, where it caused a statistically significant 58.3% (F = 14.18; <i>p</i> = 0.002) reduction in lesion size (0.70 ± 0.03 mm) when compared with negative control (1.2 ± 0.3 mm).https://www.mdpi.com/1424-8247/15/8/1005cutaneous leishmaniasisdrug assayparasitic diseasesand fliesBALB/c mice |
| spellingShingle | Sayyed Ibrahim Shah Fazli Nasir Nadia Shamshad Malik Muhammad Alamzeb Muhammad Abbas Inayat Ur Rehman Fazli Khuda Yasir Shah Khang Weh Goh Alam Zeb Long Chiau Ming Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>) Pharmaceuticals cutaneous leishmaniasis drug assay parasitic disease sand flies BALB/c mice |
| title | Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>) |
| title_full | Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>) |
| title_fullStr | Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>) |
| title_full_unstemmed | Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>) |
| title_short | Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against <i>Leishmania tropica</i> (HTD<sub>7</sub>) |
| title_sort | efficacy evaluation of 10 hydroxy chondrofoline and tafenoquine against i leishmania tropica i htd sub 7 sub |
| topic | cutaneous leishmaniasis drug assay parasitic disease sand flies BALB/c mice |
| url | https://www.mdpi.com/1424-8247/15/8/1005 |
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