| Abstract: |
Ribonucleotide reductase (RR) is the rate-limiting enzyme for de novo formation of deoxyribonucleotides and plays an important role in DNA synthesis and cell replication. Its activity is closely related to malignant transformation and tumor cell proliferation. Therefore, it is considered to be a promising target for cancer chemotherapy. Aminohydroxyguanidine possesses a similar pharmacophore to that of hydroxyurea, which is a known RR inhibitor and is, clinically used as an anticancer drug. Thus, aminohydroxyguanidine derivatives with the N-OH guanidine as a bioisosteric essential pharmacophore group were designed and developed to improve antitumor/antiviral activities. In this paper, fourteen new Schiff bases of aminohydroxyguanidine tosylate with a wide range of physicochemical properties have been synthesized and tested together with seven known related compounds for their cytotoxicities against tumor cells. Statistically significant correlation is obtained between the biological activity and the physicochemical properties by quantitative structure-activity relationship (QSAR) analysis. Among the parameters examined, the presence of an ortho-hydroxy group on the benzene ring, or isoquinoline, or furan ring as represented by an indicator variable (I), lipophilicity (log P), and dipole moment (mu) are important factors contributing to antitumor activity. |
