Hydroxyurea (HU) is a simple organic compound currently used as a cancer chemotherapeutic agent. It acts specifically on the S-phase of the cell cycle by inhibiting the enzyme ribonucleoside diphosphate reductase, thereby hindering the reductive conversion of ribonucleotides to deoxyribonucleotides and thus limiting de novo DNA synthesis. HU is employed in hemotological settings as a first-line treatment of myeloproliferative disorders, such as polycythemia vera, essential thrombocythemia and primary myelofibrosis, apart from having a vital role in combination therapy for management of malignant melanoma, head and neck cancers and brain tumors. It offers an advantage that the patient may take this drug on an ambulatory basis with minimum clinical toxicity, while some of its limitations include gastrointestinal disturbance and bone marrow depression. This review will summarize and present the overall effects of HU and its combination therapy as an anticancer agent.
Among bicyclic non-aromatic nitrogen heterocycles, phthalimides are an interesting class of compounds with a large range of applications. Phthalimide contains an imide functional group and may be considered as nitrogen analogues of anhydrides or as diacyl derivatives of ammonia. They are lipophilic and neutral compounds and can therefore easily cross biological membranes in vivo and showing different pharmacological activities. In the present work compounds containing phthalimide subunit have been described as a scaffold to design new prototypes drug candidates with different biological activities and are used in different diseases as, for example AIDS, tumor, diabetes, multiple myeloma, convulsion, inflammation, pain, bacterial infection among others.
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