Small-molecules isoxazole and isothiazole adjuvants in combination with first-line antitumor drugs in chemotherapy of neuroepithelial tumors

Chemotherapy remains one of the main options for cancer treatment. But the accompanying side effects often have a strong impact on the patient’s body condition and seriously disrupt their quality of life. Using of synergistic adjuvants in combination with therapeutic drugs may be an option to solve this problem. We found that some small-molecule isoxazole and isothiazole derivatives can act in this way. They enhance the effect of first-line antitumor drugs cisplatin, temobel, cytarabine against neuroepithelial tumors like glioma C6 or medulloblastoma. Addition of adjuvante in non-active dose to a reduced dose of toxic chemotherapy drug allows to achieve higher level of tumor cell death in vitro than the chemotherapy itself causes at this dose. We decided to begin the explanation of this phenomenon with a quantum chemical study of the interaction of morpholinium and 4-methylpiperazinium 4,5-dichloroisothiazol-3-carboxylates with cisplatin. DFT calculations showed that these compounds interact with cisplatin, which leads to a redistribution of electron density and an increase in the dipole moment. We assume that due to it the resulting system has increased bioactivity, which enhances the efficiency of its interaction with DNA. The data obtained are the basis for the search and design of new effective adjuvants.