BACKGROUND: Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties. MATERIALS AND METHODS: Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide. RESULTS: The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin. CONCLUSION: These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.
BACKGROUND:Hydantoin derivatives possess a variety of biochemical and pharmacological properties. Although hydantoin compounds are studied extensively, there are not many studies that investigate their anticancer properties. MATERIALS AND METHODS: Thirty hydantoin compounds were evaluated for their efflux modulating effects in cancer cells using a rhodamine 123 accumulation assay and real-time fluorometry based on the intracellular accumulation of ethidium bromide. RESULTS: The 30 derivatives were screened by real-time fluorometry for rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9, BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW-15b and JH-63 showed synergistic effect with doxorubicin on mouselymphoma cells. Furthermore, compound SZ-7 had indifferent effect with doxorubicin. CONCLUSION: These results indicated the role of chemical modifications within the hydantoin ring for its potential inhibition of the ABCB1 transporter. The most active structures contained aromatic substituents as well as some tertiary amine fragments.