In Silico and In Vitro Studies of 4-Hydroxycoumarin-Based Heterocyclic Enamines as Potential Anti-Tumor Agents

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 15; p. 5828
• Main Authors: Assad, Mediha, Paracha, Rizwan Nasir, Siddique, Abu Bakar, Shaheen, Muhammad Ashraf, Ahmad, Nadeem, Mustaqeem, Muhammad, Kanwal, Fariha, Mustafa, Muhammad Zia Ul, Rehman, Muhammad Fayyaz Ur, Fatima, Sumaya, Lu, Changrui
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2023; MDPI
• Subjects: anti-tumor; Antimitotic agents; Antineoplastic agents; Cancer therapies; Cell cycle; Cell growth; coumarin; Drugs; enamines; Enzymes; Force and energy; Heterocyclic compounds; hydroxycoumarin; Kinases; Liver cancer; Protein binding; Proteins; Spectrum analysis; Tumors; Germany; Pakistan; anti-tumor; enamines; coumarin; hydroxycoumarin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28155828

The present study reports the one-step synthesis of several 3-formyl-4-hydroxycouramin-derived enamines ( - ) in good yields (65-94%). The characterization of the synthesized compounds was carried out via advanced analytical and spectroscopic techniques, such as melting point, electron impact mass spectrometry (EI-MS), H-NMR, C-NMR, elemental analysis, FTIR, and UV-Visible spectroscopy. The reaction conditions were optimized, and the maximum yield was obtained at 3-4 h of reflux of the reactants, using 2-butanol as a solvent. The potato disc tumor assay was used to assess -induced tumors to evaluate the anti-tumor activities of compounds ( - ), using Vinblastine as a standard drug. The compound showed the lowest IC value (1.12 ± 0.2), which is even better than standard Vinblastine (IC 7.5 ± 0.6). For further insight into their drug actions, an in silico docking of the compounds was also carried out against the CDK-8 protein. The binding energy values of compounds were found to agree with the experimental results. The compounds and showed the best affinities toward protein, with a binding energy value of -6.8 kcal/mol.