Multidrug resistance is the dominant obstacle to effective chemotherapy for malignant neoplasms. It is well known that neoplastic cells use a wide range of adaptive mechanisms to form and maintain resistance against antitumor agents, which makes it urgent to identify promising therapies to solve this problem. Hydroxamic acids are biologically active compounds and in recent years have been actively considered to be potentially promising drugs of various pharmacological applications. In this paper, we synthesized a number of hydroxamic acids containing a p-substituted cinnamic acid core and bearing bicyclic pinane fragments, including derivatives of (−)-myrtenol, (+)-myrtenol and (−)-nopol, as a Cap-group. Among the synthesized compounds, the most promising hydroxamic acid was identified, containing a fragment of (−)-nopol in the Cap group18c. This compound synergizes with cisplatin to increase its anticancer effect and overcomes cisplatin resistance, which may be associated with the inhibition of histone deacetylase 1 and glycolytic function. Taken together, our results demonstrate that the use of hydroxamic acids with a bicyclic pinane backbone can be considered to be an effective approach to the eradication of tumor cells and overcoming drug resistance in the treatment of malignant neoplasms.
多药耐药性是恶性肿瘤有效化疗的主要障碍。众所周知，肿瘤细胞通过多种适应性机制形成并维持对抗肿瘤药物的耐药性，这使得寻找有前景的疗法以解决该问题显得尤为迫切。羟肟酸是一类具有生物活性的化合物，近年来被广泛认为在多种药理应用中具有潜在前景。本文合成了一系列含有对位取代肉桂酸核心结构、并带有双环蒎烷片段（包括以(−)-桃金娘烯醇、(+)-桃金娘烯醇及(−)-诺卜醇衍生物作为Cap基团）的羟肟酸类化合物。在合成的化合物中，Cap基团含有(−)-诺卜醇片段的羟肟酸18c展现出最佳潜力。该化合物与顺铂协同作用增强其抗癌效果，并能克服顺铂耐药性，其作用机制可能与抑制组蛋白去乙酰化酶1及糖酵解功能相关。综上所述，我们的研究结果表明，在恶性肿瘤治疗中，使用具有双环蒎烷骨架的羟肟酸可被视为清除肿瘤细胞并克服耐药性的有效策略。
肿瘤(癌症)患者之家