Independent Researcher, Chammünsterstr. 47, D-81827 München, Bavaria, Germany.
Molecules. 2024 Feb 19;29(4):914. doi: 10.3390/molecules29040914.
I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer's effect characterized by a defective mitochondrial aerobic respiration, substituted by cytosolic aerobic fermentation/glycolysis of D-(+)-glucose into L-(+)-lactic acid. The two essentially new drugs, compound [] and compound (), represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound represents a covalent combination of compound and compound (). The intermediate drug compound is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 's structure was determined using X-ray crystallography. Compound and compound were active in vitro versus 60 human cancer cell lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell testing. Compound and compound not only stop the growth of cancer cells to ±0% (cancerostatic effect) but completely kill nearly all 60 cancer cells to a level of almost -100% (tumoricidal effect). Compound and compound induce mitochondrial apoptosis (under cytochrome release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function, which results in a decrease in cancer's dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21/p21.
我提出了一种新的策略，利用两种完全新颖的药物化合物来彻底抑制人类癌症，这两种药物化合物利用了癌症的特征效应，即线粒体有氧呼吸缺陷，被细胞质有氧发酵/葡萄糖转化为 L-(+)-乳酸所取代。这两种基本的新药，化合物 [] 和化合物 ()，代表了新的高度对称的四叶桨形聚铵阳离子。高度有效的体外抗肿瘤药物化合物代表了化合物和化合物的共价结合 ()。中间药物化合物是从秋水仙碱合成的全新的秋水仙碱类似物衍生物。化合物的结构通过 X 射线晶体学确定。化合物和化合物在体外对国立癌症研究所（NCI）发展治疗学计划（DTP）的 60 个人类癌细胞系具有活性 60-癌细胞测试。化合物和化合物不仅停止癌细胞的生长到±0%（抗癌作用），而且几乎完全杀死所有 60 个癌细胞到几乎-100%（杀肿瘤作用）的水平。化合物和化合物通过（重新）激活（在大多数癌症中受损）p53 功能，诱导所有测试的癌细胞中的线粒体凋亡（细胞色素释放下），导致癌细胞失调的细胞周期蛋白 D1 减少，并诱导细胞周期停滞的细胞周期蛋白依赖性激酶抑制剂 p21/p21。
