The selective cytotoxicity of new triazene compounds to human melanoma cells

Sousa, Ana Catarina; Santos, Fábio M. F.; Gaspar, Maria Manuela; Calado, Susana; Pereira, João D.; Mendes, Eduarda; Francisco, Ana Paula; Perry, Maria de Jesus

doi:10.1016/j.bmc.2017.04.049

Cited by 16 publications

(15 citation statements)

References 31 publications

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“…In addition, a correlation between higher cytotoxicity and higher tyrosinase activity was achieved, indicating a tyrosinase-dependent activation mechanism of the prodrugs [133]. In the latest work of Sousa and colleagues (2017) [140], a new series of triazene derivatives (triazene hybrid molecules) with different physicochemical properties were synthetized. These compounds were chemically stable in physiologic milieu and, when in contact with tyrosinase, the alkylating moiety was released.…”

Section: Advancing Melanoma Systemic Treatment—potential Targets Amentioning

confidence: 99%

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Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

2019

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Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosinase. In addition, the role of nanotechnology as a valuable strategy to effectively deliver selective drugs is emphasized, either incorporating/encapsulating synthetic molecules or natural-derived compounds in lipid-based nanosystems such as liposomes. Nanoformulated compounds have been explored for their improved anticancer activity against melanoma and promising results have been obtained. Indeed, they displayed improved physicochemical properties and higher accumulation in tumoral tissues, which potentiated the efficacy of the compounds in pre-clinical experiments. Overall, these experiments opened new doors for the discovery and development of more effective drug formulations for melanoma treatment.

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Section: Advancing Melanoma Systemic Treatment—potential Targets Amentioning

confidence: 99%

“…Remarkably, two of these derivatives were demonstrated to be more cytotoxic than temozolomide. Moreover, low toxicity towards healthy human keratinocytes (HaCaT) was observed, reinforcing the strong potential of this strategy for melanoma treatment [140].…”

Section: Advancing Melanoma Systemic Treatment—potential Targets Amentioning

confidence: 99%

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

2019

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“…In industry, they can be used as chemical and biological reagents 13,14 and in organic synthesis [15][16][17] . The pharmaceutical industry has invested in studies on action against microorganisms 18,19 , functioning as appetite reducers 20,21 , anticancer agents [22][23][24][25][26] such as melanoma-specific 25 and primary brain tumors 28 therapeutics, fluorescence sensing agents 29 , mutagenic factors 12 , and having diabetic, anti-inflammatory, and antioxidant 27 activities; triazenes also exhibit biological and environmental activities 6,[30][31][32][33] .…”

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Assessment of the biological potential of diaryltriazene-derived triazene compounds

Figueiredo

Filho

Sodré

et al. 2021

Sci Rep

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In the present study, novel, 1,3-diaryltriazene-derived triazene compounds were synthesized and tested. Triazenes are versatile and belong to a group of alkylating agents with interesting physicochemical properties and proven biological activities. This study describes the synthesis, molecular and crystalline structure, biological activity evaluation, and antifungal and antimicrobial potentials of 1,3-bis(X-methoxy-Y-nitrophenyl)triazenes [X = 2 and 5; Y = 4 and 5]. The antimicrobial and antifungal activities of the compounds were tested by evaluating the sensitivity of bacteria (American Type Culture Collection, ATCC) and clinical isolates to their solutions using standardized microbiological assays, cytotoxicity evaluation, and ecotoxicity tests. The antimicrobial potentials of triazenes were determined according to their minimum inhibitory concentrations (MICs); these compounds were active against gram-positive and gram-negative bacteria, with low MIC values. The most surprising result was obtained for T3 having the effective MIC of 9.937 µg/mL and antifungal activity against Candida albicans ATCC 90028, C. parapsilosis ATCC 22019, and C. tropicallis IC. To the best of our knowledge, this study is the first to report promising activities of triazene compounds against yeast and filamentous fungi. The results showed the potential utility of triazenes as agents affecting selected resistant bacterial and fungal strains.

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“…Amides 2 with longer alkyl chains separating the triazene and the phenol (n = 4) are more stable and remain undecomposed for more than 10 days in PBS. 15 Overall, comparing the reactivities of hybrids 11a−e and 13a−f confirmed that urea derivatives are more stable than amides in PBS at 37 °C.…”

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confidence: 75%

Sulfur Analogues of Tyrosine in the Development of Triazene Hybrid Compounds: A New Strategy against Melanoma

Granada

Mendes

Perry

et al. 2021

ACS Med. Chem. Lett.

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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-S-cysteaminylphenol (4-S-CAP, 10), with immunomodulatory properties and specific melanocytotoxic activity, and triazene 4, with DNA alkylating properties. The design of these compounds aims to achieve selective activation by the enzyme tyrosinase overexpressed in melanoma cells. Compounds 11a−e, 13a, and 13b were found to be excellent tyrosinase substrates (0.5 min ≤ t 1/2 ≤ 3.7 min). Furthermore, derivatives 11 and 13 were evaluated for their molecular properties, hepatotoxicity, in vivo 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 10 may be an important component for these strategies that use a metabolic pathway of melanin synthesis. Molecular hybridization of 10 with triazenes 4 renders the hybrids (11 and 13) unexpectedly devoid of hepatotoxicity while maintaining cytotoxic activity in malignant cells.

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The selective cytotoxicity of new triazene compounds to human melanoma cells

Cited by 16 publications

References 31 publications

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma

Assessment of the biological potential of diaryltriazene-derived triazene compounds

Sulfur Analogues of Tyrosine in the Development of Triazene Hybrid Compounds: A New Strategy against Melanoma

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