{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T17:23:37Z","timestamp":1787246617428,"version":"build-2736575974"},"reference-count":74,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU funding","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"RASLR7\/07project","award":["F73C22001570002"],"award-info":[{"award-number":["F73C22001570002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>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\u00a0(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 \u221233.41, \u22129.29, \u22128.37, and \u22124.27 kcal\/mol for the predicted L. major squalene monooxygenase\u2013HPip-DC, bovine cytochrome bc1\u2013DiFiD (2,4-difluorophenyl derivative), RNase H\u2013HPip-4NO (4-nitrophenyl derivative), and RNase H\u2013HPip-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.<\/jats:p>","DOI":"10.3390\/pathogens15080876","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro and In Silico Evaluation of the Anti-Infective Potential of EF24-Analogous Curcuminoids: Antiprotozoal Activity and HIV-1 Ribonuclease H Inhibition"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-5929","authenticated-orcid":false,"given":"Tariq A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"},{"name":"Department of Pharmacology and Toxicology, Institute for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-1050","authenticated-orcid":false,"given":"Ibrahim S.","family":"Al Nasr","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-995X","authenticated-orcid":false,"given":"Waleed S.","family":"Koko","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3498-797X","authenticated-orcid":false,"given":"Kamal A.","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah 51452, Saudi 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