Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds

Abdulsalam A.M. Alkhaldi, Harry P. de Koning, Bukhari Syed Nasir Abbas

Research output: Contribution to journalArticle

Abstract

Background: Human African Trypanosomiasis (HAT) and leishmaniasis are two of the most neglected challenging tropical diseases, caused by the kinetoplastid parasites Trypanosoma and Leishmania species, respectively. For both of these complex disease spectra, treatment options are limited and threatened by drug resistance, justifying urgent new drug discovery efforts. Purpose: In the present study we investigated the antitrypanosomal and antileishmanial activity of a series of 21 symmetrical α,β-unsaturated carbonyl-based compounds, each featuring two 3-methoxybenzene attached to a central cyclohexanone, tetrahydro-4-pyranone scaffold or 4-piperidone ring. Structure-activity relationships were explored with respect to substitution on positions 3, 4 and 6 of the terminal 3-methoxybenzyl groups, and seven types of central ring. Results: Compounds 3a, 3o, 3s and 3t, showed broad anti-kinetoplastid activity against all species and strains tested. Conclusion: Compound 3o featuring N-methyl-4-piperidone was found to be the most potent analog and therefore can serve as a potential lead for the development of new drug candidates for trypanosomiasis and leishmaniasis.

Original languageEnglish
Pages (from-to)1179-1185
Number of pages7
JournalDrug Design, Development and Therapy
Volume13
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Fingerprint

Piperidones
Leishmaniasis
African Trypanosomiasis
Trypanosoma
Trypanosomiasis
Leishmania
Drug Discovery
Structure-Activity Relationship
Drug Resistance
Parasites
Pharmaceutical Preparations

Keywords

  • -α, β-unsaturated carbonyl-based compounds
  • Cyclohexanone
  • Piperidine
  • Protozoan parasites
  • Sleeping sickness

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds. / Alkhaldi, Abdulsalam A.M.; de Koning, Harry P.; Syed Nasir Abbas, Bukhari.

In: Drug Design, Development and Therapy, Vol. 13, 01.01.2019, p. 1179-1185.

Research output: Contribution to journalArticle

Alkhaldi, Abdulsalam A.M. ; de Koning, Harry P. ; Syed Nasir Abbas, Bukhari. / Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds. In: Drug Design, Development and Therapy. 2019 ; Vol. 13. pp. 1179-1185.
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