Evaluation of the Antiparasitic and Antifungal Activities of Synthetic Piperlongumine-Type Cinnamide Derivatives : Booster Effect by Halogen Substituents

DOI zum Zitieren der Version auf EPub Bayreuth: https://doi.org/10.15495/EPub_UBT_00007259
URN to cite this document: urn:nbn:de:bvb:703-epub-7259-9

Title data

Khan, Tariq A. ; Al Nasr, Ibrahim S. ; Koko, Waleed S. ; Ma, Jingyi ; Eckert, Simon ; Brehm, Lucas ; Ben Said, Ridha ; Daoud, Ismail ; Hanachi, Riadh ; Rahali, Seyfeddine ; van de Sande, Wendy W. J. ; Ersfeld, Klaus ; Schobert, Rainer ; Biersack, Bernhard:
Evaluation of the Antiparasitic and Antifungal Activities of Synthetic Piperlongumine-Type Cinnamide Derivatives : Booster Effect by Halogen Substituents.
In: ChemMedChem. Vol. 18 (2023) Issue 12 . - e202300132.
ISSN 1860-7187
DOI der Verlagsversion: https://doi.org/10.1002/cmdc.202300132

	Format: PDF Name: ChemMedChem - 2023 - Khan - Evaluation of the Antiparasitic and Antifungal Activities of Synthetic Piperlongumine‐Type.pdf Version: Published Version Available under License Creative Commons BY-NC 4.0: Attribution, Noncommercial
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Abstract

Abstract A series of synthetic N-acylpyrrolidone and -piperidone derivatives of the natural alkaloid piperlongumine were prepared and tested for their activities against Leishmania major and Toxoplasma gondii parasites. Replacement of one of the aryl meta-methoxy groups by halogens such as chlorine, bromine and iodine led to distinctly increased antiparasitic activities. For instance, the new bromo- and iodo-substituted compounds 3 b/c and 4 b/c showed strong activity against L. major promastigotes (IC50=4.5–5.8 μM). Their activities against L. major amastigotes were moderate. In addition, the new compounds 3 b, 3 c, and 4 a–c exhibited high activity against T. gondii parasites (IC50=2.0–3.5 μM) with considerable selectivities when taking their effects on non-malignant Vero cells into account. Notable antitrypanosomal activity against Trypanosoma brucei was also found for 4 b. Antifungal activity against Madurella mycetomatis was observed for compound 4 c at higher doses. Quantitative structure-activity relationship (QSAR) studies were carried out, and docking calculations of test compounds bound to tubulin revealed binding differences between the 2-pyrrolidone and 2-piperidone derivatives. Microtubules-destabilizing effects were observed for 4 b in T. b. brucei cells.

Further data

Item Type:	Article in a journal
Keywords:	Piperlongumine; Halogen; Antiparasitic drugs; Mycetoma; Neglected tropical diseases
DDC Subjects:	500 Science > 500 Natural sciences 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology
Institutions of the University:	Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Professor Genetics > Professor Genetics - Univ.-Prof. Dr. Klaus Ersfeld Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Organic Chemistry I - Univ.-Prof. Dr. Rainer Schobert Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Professor Genetics Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Language:	English
Originates at UBT:	Yes
URN:	urn:nbn:de:bvb:703-epub-7259-9
Date Deposited:	24 Oct 2023 05:35
Last Modified:	24 Oct 2023 05:35
URI:	https://epub.uni-bayreuth.de/id/eprint/7259

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