Newly synthesized (R)-carvone-derived 1,2,3-triazoles: structural, mechanistic, cytotoxic and molecular docking...

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Computational Chemistry

Background:

• Natural products like (R)-carvone serve as valuable starting materials for synthesizing novel bioactive compounds.
• 1,2,3-triazole derivatives are a class of heterocyclic compounds with diverse pharmacological properties.
• Developing efficient synthetic routes to new anticancer agents is a critical area of research.

Purpose of the Study:

• To synthesize novel 1,2,3-triazole derivatives from natural (R)-carvone.
• To evaluate the cytotoxic activity of the synthesized compounds against human cancer cell lines.
• To investigate the reaction regioselectivity and electronic properties using computational methods.

Main Methods:

• Synthesis of 1,2,3-triazole derivatives from (R)-carvone.
• Characterization using 1H and 13C NMR and HRMS.
• Cytotoxicity assessment via MTT viability assays.
• Density Functional Theory (DFT) calculations (B3LYP/6-311+G(d,p)) for structural and electronic analysis.
• Molecular docking and molecular dynamics simulations.

Main Results:

• Several 1,2,3-triazole derivatives were synthesized in good yields.
• Product 5 demonstrated moderate antitumor activity with IC50 values in the micromolar range against HT-1080, A-549, and MCF-7 cells.
• DFT calculations elucidated the regioselectivity of the condensation reaction and electronic properties (HOMO/LUMO orbitals).
• Computational studies (docking and dynamics) corroborated experimental findings and confirmed complex stability during anti-apoptotic protein inhibition.

Conclusions:

• The study successfully synthesized novel monoterpenic 1,2,3-triazole derivatives from (R)-carvone.
• Compound 5 shows promising medium antitumor activity, warranting further investigation.
• DFT and molecular modeling provide valuable insights into the structure-activity relationships and mechanism of action.