Birar Vishal C, Zaid Gene, Blagg Brian S J
Department of Chemistry and Biochemistry, University of Notre Dame, IN 46556, USA.
Genzada Pharmaceuticals, LLC, 205 S. Broadway, Sterling, KS 67579, USA.
Tetrahedron Lett. 2021 Jun 8;73. doi: 10.1016/j.tetlet.2021.153139. Epub 2021 May 1.
Herbal medicine is used as a complement to modern medicine for the treatment of human diseases suchas cancer, inflammation, and diabetes. Nutraceutical components in foods such as vanillin produceantioxidant and anticancer activities and many of these produce minimal adverse effects in humans.Therefore, strategies that combine both herbal medicine and nutraceutical components could producecompounds that exhibit reduced toxicity. Recently, we developed GZ16.007, which is a combination ofharmaline and curcumin that is currently undergoing clinical evaluation for the treatment of cancer. Incontrast to the utilization of curcumin, we report herein the synthesis of a novel scaffold that utilizes har-maline and vanillin as nutraceutical components to form a newly identified anti-cancer scaffold. It wasdetermined that the inclusion of two molecules of harmaline and a single equivalent of vanillin produceda dimeric product that was active against various human cancer cell lines. The synthesis, evaluation andpreliminary SAR studies for the dimeric scaffold is discussed herein.
草药被用作现代医学的补充，用于治疗人类疾病，如癌症、炎症和糖尿病。食品中的营养成分如香草醛具有抗氧化和抗癌活性，并且其中许多对人类产生的不良反应极小。因此，将草药和营养成分相结合的策略可能会产生毒性降低的化合物。最近，我们开发了GZ16.007，它是哈尔满和姜黄素的组合，目前正在进行癌症治疗的临床评估。与姜黄素的使用不同，我们在此报告一种新型支架的合成，该支架利用哈尔满和香草醛作为营养成分，形成一种新鉴定的抗癌支架。已确定包含两分子哈尔满和一当量香草醛会产生一种对多种人类癌细胞系有活性的二聚体产物。本文讨论了二聚体支架的合成、评估和初步构效关系研究。
