Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives

Ayanda I Zulu; Ogunyemi O Oderinlo; Cuan Kruger; Michelle Isaacs; Heinrich C Hoppe; Vincent J Smith; Clinton G L Veale; Setshaba D Khanye

doi:10.3390/molecules25071668

Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives

Molecules. 2020 Apr 4;25(7):1668. doi: 10.3390/molecules25071668.

Authors

Ayanda I Zulu¹, Ogunyemi O Oderinlo¹, Cuan Kruger¹, Michelle Isaacs², Heinrich C Hoppe^{2

3}, Vincent J Smith^{1

2}, Clinton G L Veale^{4

5}, Setshaba D Khanye^{1

2

5}

Affiliations

¹ Department of Chemistry, Faculty of Science, Rhodes University, Grahamstown 6140, South Africa.
² Centre for Chemico and Biomedicinal Research, Rhodes University, Grahamstown 6140, South Africa.
³ Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Grahamstown 6140, South Africa.
⁴ School of Chemistry and Physics, Pietermaritzburg Campus, University of KwaZulu-Natal, Private Bag X01, Scottsville 3209, South Africa.
⁵ Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Rhodes University, Grahamstown 6140, South Africa.

Abstract

With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC₅₀ values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.

Keywords: Trypanosoma brucei; arylpyrrole; chalcones; molecular hybridization; trypanosomiasis.

MeSH terms

Cell Proliferation
Chalcones / chemical synthesis*
Chalcones / chemistry
Chalcones / pharmacology
Crystallography, X-Ray
HeLa Cells
Humans
Inhibitory Concentration 50
Molecular Structure
Pyrroles / chemical synthesis*
Pyrroles / chemistry
Pyrroles / pharmacology
Structure-Activity Relationship
Trypanocidal Agents / chemical synthesis*
Trypanocidal Agents / chemistry
Trypanocidal Agents / pharmacology
Trypanosoma brucei brucei / drug effects*

Substances

Chalcones
Pyrroles
Trypanocidal Agents

Grants and funding

107270/South African National Research Foundation