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Volume 94
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10.3390/scipharm94020048
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Article

2,4-Bis{4-[(dialkylaminoalkyl)aminomethyl]phenyl}-7-substituted-7H-pyrrolo[2,3-d]pyrimidine Derivatives: Synthesis and Biological Evaluation as Novel Antiprotozoal Agents by Potentially Targeting G-Quadruplex

by
Jean Guillon
1,*,
Solène Savrimoutou
1,
Patrice Agnamey
2,
Vittoria Milano
1,
Céline Damiani
2,
Luisa Ronga
3,
Marie Hanot
2,
Sandra Albenque
1,
Tshering Zangmo
3,
Sarah Monic
1,4,
Noël Pinaud
5,
Lindita Lari
1,
Mathieu Marchivie
6,
Stéphane Moreau
1,
Jean-Louis Mergny
7,
Serge Moukha
8,9,
Pascale Dozolme
8,9,
Clotilde Boudot
10,
Bertrand Courtioux
10,
Anita Cohen
11 and
Pascal Sonnet
2,*add Show full author list remove Hide full author list
1
Faculty of Pharmacy, University of Bordeaux, CNRS, INSERM, ARNA, UMR 5320, U1212, F-33076 Bordeaux, France
2
Faculty of Pharmacy, Agents Infectieux, Résistance et Chimiothérapie (AGIR), UR 4294, University of Picardie Jules Verne, F-80037 Amiens, France
3
IPREM (Institut des Sciences Analytiques et de Physico-Chimie Pour l’Environnement et les Matériaux), Université de Pau et des Pays de l’Adour, E2S UPPA, CNRS, UMR 5254, F-64053 Pau cedex 09, France
4
MFP, University of Bordeaux, CNRS, UMR 5234, F-33076 Bordeaux, France
5
ISM, Bordeaux INP, University of Bordeaux, CNRS, UMR 5255, F-33400 Talence, France
6
UMR 5026, University of Bordeaux, CNRS, Bordeaux-INP, ICMCB, F-33608 Pessac, France
7
Laboratoire d’Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, F-91120 Palaiseau, France
8
Centre de Recherche Cardio-Thoracique de Bordeaux (CRCTB), UMR U1045 INSERM, PTIB—Hôpital Xavier Arnozan, F-33600 Pessac, France
9
INRAE Bordeaux Aquitaine, F-33140 Villenave-d’Ornon, France
10
Institute of Neuroepidemiology and Tropical Neurology, Université de Limoges, INSERM U1094, F-87025 Limoges, France
11
Faculty of Pharmacy, University of Aix-Marseille, IRD, AP-HM, SSA, VITROME, F-13005 Marseille, France
 
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Authors to whom correspondence should be addressed.
Sci. Pharm. 2026, 94(2), 48; https://doi.org/10.3390/scipharm94020048 (registering DOI)
Submission received: 12 March 2026 / Revised: 23 April 2026 / Accepted: 3 June 2026 / Published: 9 June 2026
(This article belongs to the Special Issue Pharmaceutical Applications of Heterocyclic Compounds)
Versions Notes

Abstract

A series of substituted pyrrolo[2,3-d]pyrimidines was designed, synthesized, and evaluated in vitro against two protozoan parasites: Plasmodium falciparum and Trypanosoma brucei brucei. Pharmacological studies revealed antiprotozoal activity with IC50 values in the submicromolar to micromolar range. Additionally, the in vitro cytotoxicity of these new compounds was assessed using human HepG2 cells. Among them, the pyrrolopyrimidine derivative 1d emerged as the most potent antimalarial compound, exhibiting a selectivity index (SI) of 600.81 against the P. falciparum chloroquine-resistant W2 strain. For the chloroquine-sensitive 3D7 strain, the most notable selectivity index (SI) was observed for pyrrolo[2,3-d]pyrimidine 1c, with a value of approximately 123. Furthermore, compound 1b demonstrated the most interesting activity against Trypanosoma brucei brucei, with an SI of 39.52, marking it as a promising trypanocidal agent. FRET melting assays confirmed that these nitrogen-containing heterocyclic compounds bind to telomeric G-quadruplexes in P. falciparum and Trypanosoma. However, no clear correlation was found between G-quadruplex binding and antiparasitic activity or selectivity, suggesting that G-quadruplex targeting is unlikely to be the main mechanism underlying cytotoxicity.
Keywords: Pyrrolopyrimidine; antimalarial activity; antitrypanosomal activity; G-quadruplex; FRET-melting Pyrrolopyrimidine; antimalarial activity; antitrypanosomal activity; G-quadruplex; FRET-melting

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MDPI and ACS Style

Guillon, J.; Savrimoutou, S.; Agnamey, P.; Milano, V.; Damiani, C.; Ronga, L.; Hanot, M.; Albenque, S.; Zangmo, T.; Monic, S.; et al. 2,4-Bis{4-[(dialkylaminoalkyl)aminomethyl]phenyl}-7-substituted-7H-pyrrolo[2,3-d]pyrimidine Derivatives: Synthesis and Biological Evaluation as Novel Antiprotozoal Agents by Potentially Targeting G-Quadruplex. Sci. Pharm. 2026, 94, 48. https://doi.org/10.3390/scipharm94020048

AMA Style

Guillon J, Savrimoutou S, Agnamey P, Milano V, Damiani C, Ronga L, Hanot M, Albenque S, Zangmo T, Monic S, et al. 2,4-Bis{4-[(dialkylaminoalkyl)aminomethyl]phenyl}-7-substituted-7H-pyrrolo[2,3-d]pyrimidine Derivatives: Synthesis and Biological Evaluation as Novel Antiprotozoal Agents by Potentially Targeting G-Quadruplex. Scientia Pharmaceutica. 2026; 94(2):48. https://doi.org/10.3390/scipharm94020048

Chicago/Turabian Style

Guillon, Jean, Solène Savrimoutou, Patrice Agnamey, Vittoria Milano, Céline Damiani, Luisa Ronga, Marie Hanot, Sandra Albenque, Tshering Zangmo, Sarah Monic, and et al. 2026. "2,4-Bis{4-[(dialkylaminoalkyl)aminomethyl]phenyl}-7-substituted-7H-pyrrolo[2,3-d]pyrimidine Derivatives: Synthesis and Biological Evaluation as Novel Antiprotozoal Agents by Potentially Targeting G-Quadruplex" Scientia Pharmaceutica 94, no. 2: 48. https://doi.org/10.3390/scipharm94020048

APA Style

Guillon, J., Savrimoutou, S., Agnamey, P., Milano, V., Damiani, C., Ronga, L., Hanot, M., Albenque, S., Zangmo, T., Monic, S., Pinaud, N., Lari, L., Marchivie, M., Moreau, S., Mergny, J.-L., Moukha, S., Dozolme, P., Boudot, C., Courtioux, B., ... Sonnet, P. (2026). 2,4-Bis{4-[(dialkylaminoalkyl)aminomethyl]phenyl}-7-substituted-7H-pyrrolo[2,3-d]pyrimidine Derivatives: Synthesis and Biological Evaluation as Novel Antiprotozoal Agents by Potentially Targeting G-Quadruplex. Scientia Pharmaceutica, 94(2), 48. https://doi.org/10.3390/scipharm94020048

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