Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Department of Biochemistry, Faculty of Science, University of Allahabad, Prayagraj 211002, India.
Int J Mol Sci. 2022 Apr 4;23(7):4007. doi: 10.3390/ijms23074007.
Bufalin and other cardiac steroids (CS) have been used for centuries for the treatment of congestive heart failure, arrhythmias, and other maladies. However, toxicity and the small therapeutic window of this family of steroids limit their use. Therefore, attempts to synthesize a potent, but less toxic, CS are of major importance. In the present study, two novel bufalin derivatives were synthesized and some of their pharmacological properties were characterized. The reaction of bufalin with Ishikawa's reagent resulted in the production of two novel bufalin derivatives: bufalin 2,3-ene and bufalin 3,4-ene. The compounds were purified with TLC and HPLC and their structure was verified with UV, NMR, and MS analyses. The biological activities of these compounds were evaluated by testing their ability to inhibit the Na, K-ATPase activity of the brain microsomal fraction to induce cytotoxic activity against the NCI-60 human tumor cell line panel and non-cancer human cells, and to increase the force of contraction of quail embryonic heart muscle cells in culture. The two steroids exhibited biological activities similar to those of other CS in the tested experimental systems, but with reduced cytotoxicity, advocating their development as drugs for the treatment of heart failure and arrhythmias.
蟾毒灵和其他强心甾类化合物（CS）已被用于治疗充血性心力衰竭、心律失常和其他疾病数百年。然而，这类甾体化合物的毒性和较小的治疗窗限制了它们的应用。因此，合成一种有效但毒性较低的 CS 是非常重要的。在本研究中，合成了两种新型蟾毒灵衍生物，并对其部分药理学特性进行了表征。蟾毒灵与 Ishikawa 试剂反应生成了两种新型蟾毒灵衍生物：蟾毒灵 2,3-烯和蟾毒灵 3,4-烯。通过 TLC 和 HPLC 对化合物进行纯化，并通过 UV、NMR 和 MS 分析验证其结构。通过测试它们抑制脑微粒体部分 Na，K-ATP 酶活性以诱导对 NCI-60 人肿瘤细胞系和非癌细胞的细胞毒性活性以及增加培养中的鹌鹑胚胎心肌细胞收缩力的能力来评估这些化合物的生物活性。这两种甾体化合物在测试的实验系统中表现出与其他 CS 相似的生物活性，但细胞毒性降低，这表明它们有希望开发成为治疗心力衰竭和心律失常的药物。
