Programa de Pós-graduação em Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, Brazil; Laboratório de Cultura Celular, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande do Sul, Brazil.
LEESH, Escola de Química e Alimentos, Universidade Federal do Rio Grande - FURG, Rio Grande 96203-900 RS, Brazil.
Bioorg Med Chem Lett. 2021 Jun 1;41:127988. doi: 10.1016/j.bmcl.2021.127988. Epub 2021 Mar 26.
Skin cancer is the most common type of cancer in Brazil, representing 30% of all cases. Among these, melanoma represents only 3% of malignant neoplasms; however, it is the most serious and has a high capacity for metastasis. For this reason, it is extremely important to identify more efficient compounds and treatments that stop or decrease the proliferation of melanoma, even in its more advanced stages. This work reports the synthesis and biological evaluation of two homologous series of pyrazoline fatty chain derivatives as potent antitumoral agents in the melanoma B16F10 cell line. Cells were treated with pyrazoline fatty chain compounds (3, 30, 300, and 3000 μM) for 0, 24, 48, and 72 h. Decreased cell viability was observed when using most compounds at different concentrations and times. The structure-activity relationship (SAR) between antitumoral activity and the number of carbons and lipophilicity, as well as the oxygen-sulfur bioisosteric exchange, was evaluated. Among the tested derivatives, the lipophilic compounds 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-carboxamide (2d) and 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-thiocarboxamide (3d) showed the best results in the B16F10 cell line, as they produced the best cell viability decrease effects. The presence of fatty unbranched undecyl chain in the molecular structure appears to be important for its antimelanoma properties.
皮肤癌是巴西最常见的癌症类型，占所有病例的 30%。在这些病例中，黑色素瘤仅占恶性肿瘤的 3%；然而，它是最严重的，具有很高的转移能力。因此，识别更有效化合物和治疗方法来阻止或减少黑色素瘤的增殖非常重要，即使在其更晚期也是如此。本工作报道了作为在黑色素瘤 B16F10 细胞系中有效的抗肿瘤剂的两个同源系列吡唑啉脂肪链衍生物的合成和生物学评价。将细胞用吡唑啉脂肪链化合物（3、30、300 和 3000 μM）处理 0、24、48 和 72 h。当使用大多数化合物在不同浓度和时间时，观察到细胞活力降低。评估了抗肿瘤活性与碳原子数和疏水性之间的结构-活性关系（SAR），以及氧-硫生物等排交换。在所测试的衍生物中，疏水性化合物 5-羟基-5-（三氟甲基）-3-十一烷基-4,5-二氢-1H-吡唑-1-甲酰胺（2d）和 5-羟基-5-（三氟甲基）-3-十一烷基-4,5-二氢-1H-吡唑-1-硫代甲酰胺（3d）在 B16F10 细胞系中表现出最佳结果，因为它们产生了最佳的细胞活力降低效果。分子结构中存在无支链十一烷基脂肪链似乎对其抗黑色素瘤特性很重要。
