Design, synthesis, and anticancer activity of novel isocryptolepine ‘aza’ type acyl thiourea derivatives via combined experimental and computational approach
Bioscience Reports, vol.46, no.1, pp.1-31, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 46 Issue: 1
- Publication Date: 2026
- Doi Number: 10.1042/bsr20253519
- Journal Name: Bioscience Reports
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
- Page Numbers: pp.1-31
- Hacettepe University Affiliated: Yes
Abstract
To identify novel tyrosinase inhibitors, a series of isocryptolepine ‘aza’ type acyl thiourea analogs (6a–6h) were designed and synthesized using a multistep strategy. Spectroscopic methods including FTIR, UV–vis, 1H NMR, 13C NMR, and EI-MS were utilized for detailed analysis of compounds. Their tyrosinase inhibitory activities were evaluated in vitro, demonstrating superior potency compared with kojic acid (IC50 = 16.83 ± 1.162 μM). The synthesized compounds exhibited IC50 values ranging from 0.832 ± 0.03 to 7.945 ± 0.63 μM, with compound 6g emerging as the most potent inhibitor (IC50 = 0.832 ± 0.03 μM). Kinetic studies revealed competitive inhibition by compound 6g, highlighting its potential as a lead candidate for treating tyrosinase-mediated hyperpigmentation. Additional evaluations showed that these compounds also effectively inhibited other enzymes involved in cancer progression, indicating their broad therapeutic potential. Molecular modeling studies against the tyrosinase enzyme (PDB: 4OUA) confirmed strong binding interactions, while structure-activity relationship analyses provided insights into their inhibitory mechanisms. Geometry optimization of the compounds, supporting their favorable molecular properties. Drug-likeness evaluations further validated the potential of these analogs as promising anti-tyrosinase agents. Overall, this study establishes compound 6g and its analogs as compelling candidates for further development in hyperpigmentation and cancer therapeutics.