Effect of The Isotiazole Adjuvants in Combination With Cisplatin in Chemotherapy of Neuroepithelial Tumors: Experimental Results and Modeling
Michels, Dominik L.
Kulchitsky, Vladimir A.
KAUST DepartmentKing Abdullah University of Science and Technology
Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
Computer Science Program
Visual Computing Center (VCC)
Permanent link to this recordhttp://hdl.handle.net/10754/677944
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AbstractChemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for selection of the optimal agent. Here we examine the system drug-adjuvant to explain observed effect in practice. We used the first line drug – cisplatin. Morpholinium and 4-methylpiperazinium 4,5-dichloro isothiazol-3-carboxylates were selected as adjuvants. The study of cisplatin – adjuvant system was carried out by quantum chemical modeling with DFT method. It turned out that adjuvants form conjugates with cisplatin that leads to relocation of frontier molecular orbitals as well as increase of conjugate’s dipole moment. It results in change of the character of interaction with DNA and increase of bioactivity of system. The data obtained are the basis for expanding the studies to include other drugs and adjuvants. Oncologists will have opportunity to use “classical” chemotherapy drugs in combination with synergists for those patients who have not been previously recommended to such treatment because of pronounced toxic side effects.
CitationPotkin, V., Pushkarchuk, A., Zamaro, A., Zhou, H., Kilin, S., Petkevich, S., Kolesnik, I., Michels, D., Lyakhov, D., & Kulchitsky, V. A. (2022). Effect of The Isotiazole Adjuvants in Combination With Cisplatin in Chemotherapy of Neuroepithelial Tumors: Experimental Results and Modeling. https://doi.org/10.21203/rs.3.rs-1358521/v1
SponsorsThis work was carried out with partly financial support from the Belarusian State Scientific Research Program “Convergence 2025”, National Academy of Sciences of Belarus. All Gaussian16 computations were performed on KAUST’s Ibex HPC, Saudi Arabia. The authors thank the KAUST Supercomputing Core Lab team for assistance with tasks execution on Skylake nodes.
PublisherResearch Square Platform LLC
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