Malignant melanoma is the major cause of death from skin cancer. Treatment of metastatic melanoma remains an enormous challenge. In this study we developed hybrid compounds and studied their potential use in malignant melanoma chemotherapy. They were designed to act by a double mechanism of action, being composed of two pharmacophores: the tyrosine sulfur analogue 4-<i>S</i>-cysteaminylphenol (4-S-CAP, <b>10</b>), with immunomodulatory properties and specific melanocytotoxic activity, and triazene <b>4</b>, with DNA alkylating properties. The design of these compounds aims to achieve selective activation by the enzyme tyrosinase overexpressed in melanoma cells. Compounds <b>11a</b>-<b>e</b>, <b>13a</b>, and <b>13b</b> were found to be excellent tyrosinase substrates (0.5 min ≤ <i>t</i> <sub>1/2</sub> ≤ 3.7 min). Furthermore, derivatives <b>11</b> and <b>13</b> were evaluated for their molecular properties, hepatotoxicity, <i>in vivo</i> toxicity profile, and assessment of cytotoxic activity in melanoma and non-melanoma cell lines. The results were compared with those obtained for temozolomide, a triazene used in melanoma therapy. It was discovered that the hybrids are selective and effective drugs, representing a valuable model for the development of new multitarget melanoma therapy. In particular, compound <b>10</b> may be an important component for these strategies that use a metabolic pathway of melanin synthesis. Molecular hybridization of <b>10</b> with triazenes <b>4</b> renders the hybrids (<b>11</b> and <b>13</b>) unexpectedly devoid of hepatotoxicity while maintaining cytotoxic activity in malignant cells.