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  3. Design and synthesis of novel halogen rich salicylanilides as potential antileishmanial agents

Design and synthesis of novel halogen rich salicylanilides as potential antileishmanial agents

  • Eur J Med Chem. 2023 Jan 15:246:114996. doi: 10.1016/j.ejmech.2022.114996.
Jhajan Lal 1,  Karthik Ramalingam 2,  Rachana Meena 1,  Shabina B Ansari 1,  Deepanshi Saxena 3,  Sidharth Chopra 4,  Neena Goyal 5,  Damodara N Reddy 6
Affiliations

Affiliations

  • 1 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research, Ghaziabad, 201002, India.
  • 2 Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Sector 10, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India.
  • 3 Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Sector 10, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India.
  • 4 Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Sector 10, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research, Ghaziabad, 201002, India.
  • 5 Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Sector 10, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research, Ghaziabad, 201002, India. Electronic address: neena_goyal@cdri.res.in.
  • 6 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Sector 10, Janakipuram Extension, Sitapur Road, Lucknow, 226031, India; Academy of Scientific and Innovative Research, Ghaziabad, 201002, India. Electronic address: damodara.reddy@cdri.res.in.
PMID: 36565533 DOI: 10.1016/j.ejmech.2022.114996
Abstract

The available therapeutic treatment for leishmaniasis is inadequate and toxic due to side effects, expensive and emergence of drug resistance. Affordable and safe antileishmanial agents are urgently needed and toward this objective, we synthesized a series of 32 novel halogen rich salicylanilides including niclosamide and oxyclozanide and investigated their antileishmanial activity against amastigotes of Leishmania donovani. In vitro data showed fifteen compounds inhibited intracellular amastigotes with an IC50 of below 5 μM and selectivity index above 10. Among 15 active compounds, 14 and 24 demonstrated better activity with an IC50 of 2.89 μM and 2.09 μM respectively and selectivity index is 18. Compound 24 exhibited significant in vivo antileishmanial efficacy and reduced 65% of the splenic Parasite load on day 28th post-treatment in the experimental visceral leishmaniasis golden hamster model. The data suggest that 24 can be a promising lead candidate possessing potential to be developed into a leishmanial drug candidate.

Keywords

Amastigotes; Benzanilides; L. donovani; Leishmaniasis; Niclosamide; Oxyclozanide; Salicylanilides.

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