Alcolea Verónica, Garnica Pablo, Palop Juan A, Sanmartín Carmen, González-Peñas Elena, Durán Adrián, Lizarraga Elena
Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy and Nutrition, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Department of Chemistry, Faculty of Sciences, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Molecules. 2017 Aug 8;22(8):1314. doi: 10.3390/molecules22081314.
The physicochemical properties of a compound play a crucial role in the cancer development process. In this context, polymorphism can become an important obstacle for the pharmaceutical industry because it frequently leads to the loss of therapeutic effectiveness of some drugs. Stability under manufacturing conditions is also critical to ensure no undesired degradations or transformations occur. In this study, the thermal behaviour of 40 derivatives of a series of sulphur and selenium heteroaryl compounds with potential antitumoural activity were studied. In addition, the most promising cytotoxic derivatives were analysed by a combination of differential scanning calorimetry, X-ray diffraction and thermogravimetric techniques in order to investigate their polymorphism and thermal stability. Moreover, stability under acid, alkaline and oxidative media was tested. Degradation under stress conditions as well as the presence of polymorphism was found for the compounds VA6E and VA7J, which might present a hurdle to carrying on with formulation. On the contrary, these obstacles were not found for derivative VA4J.
化合物的物理化学性质在癌症发展过程中起着至关重要的作用。在这种情况下，多晶型现象可能成为制药行业的一个重要障碍，因为它经常导致一些药物治疗效果的丧失。生产条件下的稳定性对于确保不发生不期望的降解或转化也至关重要。在本研究中，对一系列具有潜在抗肿瘤活性的硫和硒杂芳基化合物的40种衍生物的热行为进行了研究。此外，通过差示扫描量热法、X射线衍射和热重技术相结合的方法，对最有前景的细胞毒性衍生物进行了分析，以研究它们的多晶型现象和热稳定性。此外，还测试了它们在酸性、碱性和氧化介质中的稳定性。发现化合物VA6E和VA7J在应激条件下会发生降解以及存在多晶型现象，这可能会给制剂的继续研发带来障碍。相反，衍生物VA4J没有这些障碍。
