Synthesis and Biological Profiles of Some Benzimidazolyl-chalcones as Anti-leishmanial and Trypanocidal Agents
D. U. J-P. N'Guessan
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological Sciences, FHB University, 01 BP V34 Abidjan, Côte d´Ivoire.
L. A. C. Kablan
Department of Mathematics, Physics and Chemistry, UPR of Organic Chemistry, UFR of Biological Sciences, Peleforo Gon Coulibaly University, BP 1328 Korhogo, Côte d’Ivoire and Laboratory of Constitution and Reaction of Matter, UFR Structural Sciences of Matter and Technology, Félix Houphouët-Boigny University, 22 BP 582 Abidjan 22, Côte d’Ivoire.
A. Kacou
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological Sciences, FHB University, 01 BP V34 Abidjan, Côte d´Ivoire.
C. Bories
Antiparasitic Chemotherapy Laboratory, UMR BioCIS, CNRS, Paris-Saclay University, 92296 Châtenay-Malabry, France.
S. Coulibaly
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological Sciences, FHB University, 01 BP V34 Abidjan, Côte d´Ivoire.
D. Sissouma
Laboratory of Structural Organic Chemistry, UFR Structural Sciences of Matter and Technology, Félix Houphouët-Boigny University, 22 BP 582 Abidjan 22, Côte d’Ivoire.
P. M. Loiseau
Antiparasitic Chemotherapy Laboratory, UMR BioCIS, CNRS, Paris-Saclay University, 92296 Châtenay-Malabry, France.
M. Ouattara *
Department of Therapeutic Chemistry and Organic Chemistry, UFR Pharmaceutical and Biological Sciences, FHB University, 01 BP V34 Abidjan, Côte d´Ivoire.
*Author to whom correspondence should be addressed.
Abstract
Background: Benzimidazole constitutes a starting point for the development of new antiprotozoal agents since this nucleus exists in several pharmacologically significant molecules, in particular possessing antifungal, antiviral, antibacterial, and antiparasitic properties.
Objective: The present study aimed to identify a molecular hit likely to be developed as an anti-leishmanial and antitrypanosomal drug candidate.
Methods: Thus, 12 hybrids of chalcone or benzimidazolyl-arylpropenones were synthesized and screened in vitro for anti-leishmanial activity against promastigotes of Leishmania donovani. The microculture tetrazolium assay was used to determine their potential to inhibit 50% of a parasite growth (IC50).
Results: Two compounds among 5-chlorobenzimidazole-chalcones (4a and 4c), which exhibited potent activity (IC50<1 μM) against L. donovani and one derivative (4d) poorly effective against L. donovani (IC50>50 μM) were selected to check their trypanocidal activity. Lethal concentration (LC100) values of these compounds were estimated by using observations on the viability of trypomastigotes of Trypanosoma brucei brucei in MEM medium with Earle’s salts and L-glutamine. Seven of the tested compounds (4a, 4b, 4c, 4e, 4g, 4h, and 4j) showed particularly higher inhibitory activity than pentamidine (IC50= 7.6 μM) against L. donovani promastigotes with IC50 values in a range from 0.5 to 1.8 μM. In addition, the 2’-chlorine derivative (4c), displayed potent anti-trypanosomal activity comparable to those of melarsoprol, used as reference drug.
Conclusion: These results support this series of benzimidazole holding arylpropenone group in position 2 as a starting point for future optimization to get novel agents active against leishmaniasis and trypanosomiasis.
Keywords: Benzimidazole, arylpropenone, SAR, anti-leishmanial, trypanocidal