Novel Carbazole–Acylthiourea Derivatives: Synthesis, Antimicrobial, Antioxidant, Hemocompatibility, Cytotoxicity, and ADME‐Tox Profiling
5 affiliations
- 1“Carol Davila” University of Medicine and Pharmacy
- 2University of Bucharest
- 3“C.D. Nenitzescu” Institute of Organic and Supramolecular Chemistry of the Romanian Academy
- 4Babeş‐Bolyai University
- 5Carol Davila University of Medicine and Pharmacy Bucharest
Abstract
A focused series of four carprofen‐derived carbazole–acylthiourea N ‐(arylcarbamothioyl)propanamides ( 1a–d ) was synthesized by in situ generation of 2‐(6‐chloro‐9 H ‐carbazol‐2‐yl)propanoyl isothiocyanate followed by reaction with aniline, para ‐toluidine, para‐ bromoaniline, and para‐ iodoaniline, respectively. The structures were supported by FT‐IR, NMR, and APCI‐HRMS analyses. The compounds were evaluated against clinically relevant bacterial and fungal strains, complemented by antioxidant assays, hemocompatibility/antihemolysis models, cancer cell viability assays, and in silico drug‐likeness, pharmacokinetic, pharmacogenomic, and toxicity prediction. The biological profile was substituent‐dependent: 1b showed the strongest activity against Staphylococcus aureus (MIC = 0.25 mg/mL), 1a and 1c were the most active against Enterococcus faecalis (MIC = 0.31 mg/mL), while the iodophenyl derivative 1d was the most potent against Candida albicans (MIC = 0.16 mg/mL). Compounds 1b and 1c also inhibited microbial adherence in selected Gram‐positive and fungal models. Compound 1a displayed the most consistent antioxidant activity across antioxidant assays and protected erythrocytes from AAPH‐induced oxidative hemolysis. The cytotoxicity screening revealed increased sensitivity of A‐431 cells, particularly to 1b (IC50 = 13.67 µg/mL). Molecular docking revealed key binding interactions potentially underlying the observed biological activity. Overall, the integrated data identify carbazole–acylthiourea propanamides, especially 1a and 1b , as promising bioactive scaffolds for further optimization as multifunctional compounds.
Related
- Synthesis, Antioxidant Activity, In Silico Evaluation, and Cytotoxicity of Novel Polyphenolic–Methyliden–Hydrazono–Thiazole Derivatives
- In silico DFT, ADMET and molecular docking studies of novel coumarin-linked pyrazole and quinoline derivatives as antimicrobial and antioxidant agents
- Physicochemical properties, selective cytotoxicity, and hemocompatibility of silver nanoparticles biosynthesized using Schizophyllum commune extract
- Tasmannioside A, a New Eudesmane Sesquiterpene Glycoside, and Antioxidant Phenolic Derivatives from Tasmannia lanceolata
- Integrated Experimental and Computational Investigation of Fluorinated Benzoylthiourea Derivatives: Structural Characterization, Hirshfeld Surface Analysis, Antioxidant Activity, and MAO–B Inhibitory Potential for Parkinson’s Disease
BibTeX
@article{limban2026novel,
title = {{Novel Carbazole–Acylthiourea Derivatives: Synthesis, Antimicrobial, Antioxidant, Hemocompatibility, Cytotoxicity, and ADME‐Tox Profiling}},
author = {Carmen Limban and Ioana Cristina Marinaş and Mariana Carmen Chifiriuc and Miron Teodor Căproiu and Florea Dumitraşcu and Erzsébet‐Eleonóra Kapronczai and Irina Zarafu and Diana Camelia Nuţă and Petre Ioniţă and Speranţa Avram and Cătălina Mareş and Andra Maria Păun and Bogdan Mihai Cristea and Carmellina Daniela Bădiceanu and Ilinca Margareta Vlad and Maria Coandă and Delia Laura Popescu and Coralia Bleotu},
journal = {ChemistryOpen},
year = {2026},
month = oct,
doi = {10.1002/open.70258},
url = {https://europepmc.org/article/PMC/PMC13657261},
note = {CC BY},
}
RIS
TY - JOUR
TI - Novel Carbazole–Acylthiourea Derivatives: Synthesis, Antimicrobial, Antioxidant, Hemocompatibility, Cytotoxicity, and ADME‐Tox Profiling
AU - Carmen Limban
AU - Ioana Cristina Marinaş
AU - Mariana Carmen Chifiriuc
AU - Miron Teodor Căproiu
AU - Florea Dumitraşcu
AU - Erzsébet‐Eleonóra Kapronczai
AU - Irina Zarafu
AU - Diana Camelia Nuţă
AU - Petre Ioniţă
AU - Speranţa Avram
AU - Cătălina Mareş
AU - Andra Maria Păun
AU - Bogdan Mihai Cristea
AU - Carmellina Daniela Bădiceanu
AU - Ilinca Margareta Vlad
AU - Maria Coandă
AU - Delia Laura Popescu
AU - Coralia Bleotu
PY - 2026
DA - 2026/10/12
JO - ChemistryOpen
DO - 10.1002/open.70258
UR - https://europepmc.org/article/PMC/PMC13657261
AB - A focused series of four carprofen‐derived carbazole–acylthiourea N ‐(arylcarbamothioyl)propanamides ( 1a–d ) was synthesized by in situ generation of 2‐(6‐chloro‐9 H ‐carbazol‐2‐yl)propanoyl isothiocyanate followed by reaction with aniline, para ‐toluidine, para‐ bromoaniline, and para‐ iodoaniline, respectively. The structures were supported by FT‐IR, NMR, and APCI‐HRMS analyses. The compounds were evaluated against clinically relevant bacterial and fungal strains, complemented by antioxidant assays, hemocompatibility/antihemolysis models, cancer cell viability assays, and in silico drug‐likeness, pharmacokinetic, pharmacogenomic, and toxicity prediction. The biological profile was substituent‐dependent: 1b showed the strongest activity against Staphylococcus aureus (MIC = 0.25 mg/mL), 1a and 1c were the most active against Enterococcus faecalis (MIC = 0.31 mg/mL), while the iodophenyl derivative 1d was the most potent against Candida albicans (MIC = 0.16 mg/mL). Compounds 1b and 1c also inhibited microbial adherence in selected Gram‐positive and fungal models. Compound 1a displayed the most consistent antioxidant activity across antioxidant assays and protected erythrocytes from AAPH‐induced oxidative hemolysis. The cytotoxicity screening revealed increased sensitivity of A‐431 cells, particularly to 1b (IC50 = 13.67 µg/mL). Molecular docking revealed key binding interactions potentially underlying the observed biological activity. Overall, the integrated data identify carbazole–acylthiourea propanamides, especially 1a and 1b , as promising bioactive scaffolds for further optimization as multifunctional compounds.
SN - 2191-1363
ER -