In Vitro and In Vivo Evaluation of an Adamantyl-Based Phenyl Sulfonyl Acetamide against Cutaneous Leishmaniasis Models of Leishmania amazonensis

Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01188-20. doi: 10.1128/AAC.01188-20. Print 2020 Nov 17.

Abstract

Phenotypic assay against Leishmania amazonensisin vitro and in vivo led to identification of an adamantyl-based phenyl sulfonyl acetamide (compound 1) as a promising antileishmanial agent. Compound 1 inhibited the growth of intracellular forms of L. amazonensis (50% inhibitory concentration [IC50] = 4 μM) and exhibited low toxicity to host cells, with a selectivity index (SI) of >125. However, in a cutaneous leishmaniasis (CL) mouse model, compound 1 did not reduce lesions and parasite load when administered as monotherapy or when given simultaneously with a suboptimal dose of miltefosine.

Keywords: adamantyl; cutaneous leishmaniasis; experimental chemotherapy; phenyl sulfonyl acetamide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides
  • Animals
  • Antiprotozoal Agents* / pharmacology
  • Antiprotozoal Agents* / therapeutic use
  • Leishmania mexicana*
  • Leishmania*
  • Leishmaniasis, Cutaneous* / drug therapy
  • Mice
  • Mice, Inbred BALB C

Substances

  • Acetamides
  • Antiprotozoal Agents