| Autor: |
Ifeoma Ezenyi, Evanka Madan, Jhalak Singhal, Ravi Jain, Amrita Chakrabarti, Gajala Deethamvali Ghousepeer, Ramendra Pati Pandey, Ngozichukwuka Igoli, John Igoli, Shailja Singh |
| Rok vydání: |
2023 |
| Předmět: |
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| DOI: |
10.6084/m9.figshare.22925037 |
| Popis: |
Available anti-leishmanial drugs are associated with toxic side effects, necessitating the search for safe and effective alternatives. This study is focused on identifying traditional medicinal plant natural products for anti-leishmanial potential and possible mechanism of action. Compounds S and T. cordifolia residual fraction (TC-5) presented the best anti-leishmanial activity (IC50: 0.446 and 1.028 mg/ml) against promastigotes at 48 h and less cytotoxicity to THP-1 macrophages. These test agents elicited increased expression of pro-inflammatory cytokines; TNFα and IL-12. In infected untreated macrophages, NO release was suppressed but was significantly (p < 0.05) increased in infected cells treated with compound S. Importantly, Compound S was found to interact with LdTopoIIdimer in silico, resulting in a likely reduced ability of nucleic acid (dsDNA)-remodelling and, as a result, parasite proliferation in vitro. Thereby, Compound S possesses anti-leishmanial activity and this effect occurs via a Th1-mediated pro-inflammatory response. An increase in NO release and its inhibitory effect on LdTopoII may also contribute to the anti-leishmanial effect of compound S. These results show the potential of this compound as a potential starting point for the discovery of novel anti-leishmanial leads. Communicated by Ramaswamy H. Sarma |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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