In Vitro and In Silico Evaluation of the Anti-Infective Potential of EF24-Analogous Curcuminoids: Antiprotozoal Activity and HIV-1 Ribonuclease H Inhibition
Abstract
Curcumin derivatives (curcuminoids) exhibit considerable antiparasitic and antiviral activities. In this study, EF24-like bis-2-fluorobenzylidene piperidone derivatives were synthesized and evaluated for antiprotozoal activity and inhibition of the human immunodeficiency virus (HIV)-1 reverse transcriptase (RT)-associated RNase H (HIV-1 RNase H). A series of bis-arylidene piperidones and tetrahydro(thio)pyranones bearing halogen or nitro substituents were tested against Leishmania major (promastigotes and amastigotes) and Toxoplasma gondii. L. major promastigotes were the most sensitive parasitic model, with several compounds exhibiting low-nanomolar IC50 values, while ortho- or para-halogenated analogues demonstrated submicromolar activity against T. gondii. Among them, 3,4-dichlorophenyl (HPip-DC) and 4-bromophenyl (HPip-4Br) derivatives showed potent activity against L. major and HIV-1 RNase H. The entropy-uncorrected MM-GBSA effective binding energy estimates were −33.41, −9.29, −8.37, and −4.27 kcal/mol for the predicted L. major squalene monooxygenase–HPip-DC, bovine cytochrome bc1–DiFiD (2,4-difluorophenyl derivative), RNase H–HPip-4NO (4-nitrophenyl derivative), and RNase H–HPip-DC complexes, respectively. During 300 ns simulations, the ligands remained associated with their binding pockets. The Arg557 residue was crucial for HPip-4NO-mediated RNase H inhibition while the inhibitory activity of HPip-DC was much less dependent on this amino acid. These findings identify EF24-like curcuminoids with potent in vitro antiprotozoal activity and biochemical inhibition of HIV-1 RNase H. Antiviral activity was observed but confounded by host cell toxicity.
Related
- Microvesicles from Turmeric Extracts Contain Curcuminoids and Modulate Macrophage Polarization and Migration
- Green synthesis of ZnO nanoparticles using pomegranate husk extract: comparative evaluation of antioxidant, enzyme inhibition, and cytotoxic properties
- Design and Synthesis of New Derivatives of Alkaloid Lupinine: Structural Characterization, Acetylcholinesterase Inhibition Evaluation, and Molecular Modeling Study
- New thiazole/coumarin hybrids as EGFR inhibitors with potential VEGFR-2 inhibition (design, synthesis, biological evaluation, and dynamic stimulation).
- Aggregation-Driven Self-Inhibition of Grignard Reagents: Insights from DFT and Microkinetic Modeling
BibTeX
@article{khan2026vitro,
title = {{In Vitro and In Silico Evaluation of the Anti-Infective Potential of EF24-Analogous Curcuminoids: Antiprotozoal Activity and HIV-1 Ribonuclease H Inhibition}},
author = {Tariq Khan and Ibrahim Al Nasr and Waleed Koko and Kamal Qureshi and Nhat Quang Tu and Clémence Richetta and Federica Putzu and Laura Dettori and Olivier Delelis and Rainer Schobert and Angela Corona and Bernhard Biersack},
journal = {Pathogens},
year = {2026},
month = aug,
doi = {10.3390/pathogens15080876},
url = {https://hal.science/hal-05781257v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - In Vitro and In Silico Evaluation of the Anti-Infective Potential of EF24-Analogous Curcuminoids: Antiprotozoal Activity and HIV-1 Ribonuclease H Inhibition
AU - Tariq Khan
AU - Ibrahim Al Nasr
AU - Waleed Koko
AU - Kamal Qureshi
AU - Nhat Quang Tu
AU - Clémence Richetta
AU - Federica Putzu
AU - Laura Dettori
AU - Olivier Delelis
AU - Rainer Schobert
AU - Angela Corona
AU - Bernhard Biersack
PY - 2026
DA - 2026/08/20
JO - Pathogens
DO - 10.3390/pathogens15080876
UR - https://hal.science/hal-05781257v1
AB - Curcumin derivatives (curcuminoids) exhibit considerable antiparasitic and antiviral activities. In this study, EF24-like bis-2-fluorobenzylidene piperidone derivatives were synthesized and evaluated for antiprotozoal activity and inhibition of the human immunodeficiency virus (HIV)-1 reverse transcriptase (RT)-associated RNase H (HIV-1 RNase H). A series of bis-arylidene piperidones and tetrahydro(thio)pyranones bearing halogen or nitro substituents were tested against Leishmania major (promastigotes and amastigotes) and Toxoplasma gondii. L. major promastigotes were the most sensitive parasitic model, with several compounds exhibiting low-nanomolar IC50 values, while ortho- or para-halogenated analogues demonstrated submicromolar activity against T. gondii. Among them, 3,4-dichlorophenyl (HPip-DC) and 4-bromophenyl (HPip-4Br) derivatives showed potent activity against L. major and HIV-1 RNase H. The entropy-uncorrected MM-GBSA effective binding energy estimates were −33.41, −9.29, −8.37, and −4.27 kcal/mol for the predicted L. major squalene monooxygenase–HPip-DC, bovine cytochrome bc1–DiFiD (2,4-difluorophenyl derivative), RNase H–HPip-4NO (4-nitrophenyl derivative), and RNase H–HPip-DC complexes, respectively. During 300 ns simulations, the ligands remained associated with their binding pockets. The Arg557 residue was crucial for HPip-4NO-mediated RNase H inhibition while the inhibitory activity of HPip-DC was much less dependent on this amino acid. These findings identify EF24-like curcuminoids with potent in vitro antiprotozoal activity and biochemical inhibition of HIV-1 RNase H. Antiviral activity was observed but confounded by host cell toxicity.
SN - 2076-0817
ER -