1st International Conference on Chemo and BioInformatics, ICCBIKG 2021, (56-59)
AUTHOR(S) / АУТОР(И): Dušan S. Dimić, Dejan A. Milenković, Edina H. Avdović, Goran N. Kaluđerović, Jasmina M. Dimitrić Marković
E-ADRESS / Е-АДРЕСА: firstname.lastname@example.org, email@example.com,
firstname.lastname@example.org, email@example.com, firstname.lastname@example.org
ABSTRACT / САЖЕТАК:
Novel biologically active compounds can be obtained by the structural modification of coumarins. In this contribution, five new derivatives of 4-hydroxycoumarin with tyramine, octopamine, norepinephrine, 3-methoxytyramine, and dopamine were obtained. Their structures were optimized based on the previously obtained crystal structure of the 4-hydroxycoumarin-dopamine derivative. The special emphasis was put on the effect of various substituents on the structure of obtained compounds and intramolecular interactions governing the stability. To investigate their possible antitumor activity, molecular docking and molecular dynamics simulations were performed with Carbonic anhydrase, a prognostic factor in several cancers, and compared to the native ligand, 5-acetamido-1,3,4-thiadiazole- 2-sulfonamide. The results have shown that all of the coumarin-neurotransmitter derivatives bind to the active pocket of protein with the binding energies higher than for the native ligand. The main contributions to the binding energies were discussed. The Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Radius of gyration (Rg), as results of MD simulations, were used to predict the activity of compounds towards chosen protein. The highest MD binding energies were obtained for the derivatives with dopamine and 3-methoxytyramine, with the van der Waals interaction and hydrogen bonds being the most important contributors.
KEY WORDS / КЉУЧНЕ РЕЧИ:
4-hydroxycoumarin, neurotransmitter, molecular docking, carbonic anhydrase, molecular dynamics
REFERENCES / ЛИТЕРАТУРА:
- Najjar, N. Rajabi, R. Karaman, Recent Approaches to Platinum(IV) Prodrugs: A Variety of Strategies for Enhanced Delivery and Efficacy, Current Pharmaceutical Design 23 (2017) 2366- 2376
- R. Antonijević, D. M. Simijonović, E. H. Avdović, A. Ćirić, Z. D. Petrović, J. D. Marković, V. Stepanić, Z. S. Marković, Green One-Pot Synthesis of Coumarin-Hydroxybenzohydrazide Hybrids and Their Antioxidant Potency, Antioxidants 10 (2021) 1106
- S. Dimić, Z. S. Marković, L. Saso, E. H. Avdović, J. R. Đorović, I. P. Petrović, D. D. Stanisavljević, M. J. Stevanović, I. Potočňák, E. Samoľová, S. R. Trifunović, J. Dimitrić Marković, Synthesis and characterization of 3-(1-((3,4-dihydroxyphenethyl)amino )ethylidene)-chroman- 2,4-dione as potential anti-tumor agent, Oxidative medicine and cellular longevity 2019 (2019) 2069250.
- Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; et al. Gaussian 09, Revision C.01, Gaussian, Inc., Wallingford CT,