Speaker
Description
We offer a contribution to methodology of targeting important regulatory nucleic acid structures, G-quadruplexes. A model of their interaction with potentially anticancer hetero-polycyclic molecules is developed using methods of its precision computation by quantum chemistry.1 Further we use quantitative characterizations of biological activity of studied heterocycles.2 We find meaningful relationships of computed molecular energetic values, namely affinity of heterocyclic ligands to a model G-quadruplex, and experimental values of pharmacological characteristics, e.g. IC50.3 Applied quantum chemistry theories are DFT, e.g. using wB97XD/6-31G*, and explicitly correlated MO theory,1,3 e.g. in the RI-MP2 form. These types of QSAR may be significant in the quest for novel anticancer and other medications, provided G-quadruplex regulation of the key biological process is involved.
The reported research has been supported by Grant KP-06-N59/1, 15.11.2021 from the Bulgarian NSF, the allotted computer facilities of e-infrastructure of the NCHDC under Grant D01-168/28.07.2022, and Consortium Petascale Supercomputer -Bulgaria and EuroHPC supercomputer.
Keywords: G-quadruplexes, quantum chemical model, ligand affinity, cancer IC50
References:
1. Kaneti, J., et al., Biological activity of quinazoline analogues and molecular modeling of their interactions with G-quadruplexes. BBA-Gen. Subjects 2021, 1865 (1), 129773. https://doi.org/ 10.1016/j.bbagen.2020.129773.
2. Bakalova, S. M., et al., Modern Approaches to Cancer Treatment. Lecture Notes in Bioinformatics 2022, 13346, 1 – 11. https://doi.org/10.1007/978-3-031-07704-3_18
3. Kaneti. J., et al., Small Heterocyclic Ligands as Anticancer Agents: QSAR with a Model G-Quadruplex. Molecules 2022, 27 (21), 7577. https://doi.org/10.3390/molecules27217577
