ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics.

Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of , a candidate for chemotherapy, and alone and in association with commercial chemotherapeutic agents. Subsequently, the results of and were compared. Male Swiss mice were treated with doses of 12, 24, or 48 mg/kg or alone or in association with cisplatin (6 mg/kg), doxorubicin (16 mg/kg), and cyclophosphamide (100 mg/kg). Biometric parameters, DNA damage (comet and micronuclei), cell death, and splenic phagocytosis were evaluated. DNA docking was also performed to confirm the possible interactions of and with DNA. has been shown to have low genotoxic potential, increase the frequency of cell death, and activate phagocytosis. causes genomic and chromosomal damage in addition to causing cell death and activating phagocytosis. In association with chemotherapeutical agents, both and have a chemopreventive effect and, therefore, reduce the frequency of DNA damage, cell death, and splenic phagocytosis. The association of and with commercial chemotherapeutic agents increased the frequency of lymphocytes compared to chemotherapeutic agents alone. Molecular docking demonstrated that has more affinity for DNA than and its precursors ( and ). This was confirmed by the lower interaction energy of the complex (-119.83 kcal/mol). can break the DNA molecule and, therefore, its chemotherapeutic effect can be related to DNA damage. It is considered that has chemotherapeutic potential. However, it should not be used in combination with cisplatin, doxorubicin, and cyclophosphamide as it reduces the effects of these drugs.