Cycloparamide is an isosteroidal alkaloid isolated from Veratrum. It can inhibit hedgehogsignaling pathway, induce a variety of tumor apoptosis, and has no effect on the growth of normal somatic cells. In recent years, some in vitro experimental results show that the combination of cyclophosphamide with anti-tumor drugs (such as paclitaxel, tyrosine kinase inhibitor gefitinib, etc.) and radiotherapy can significantly enhance their killing effect on tumor cells. Therefore, as a potential anti-tumor drug, it has attracted extensive attention at home and abroad, and related research is also being carried out.
1. Pharmacological action
In addition to teratogenicity, it has been found that cycloparamide has significant inhibitory activity against a variety of tumors, such as maternal medullary cell tumor, basal cell carcinoma, glioma, rhabdomyosarcoma, small cell lung cancer, digestive tract tumors, mainly including gastric cancer, breast cancer, pancreatic cancer, prostate cancer, etc. In addition, studies have reported that cyclophosphamide can inhibit red blood cell differentiation, destroy spermatic cord during embryonic testicular formation, and has curative effects on hypertension, heart disease and psoriasis.
2. Mechanism of action
The preparation and anti-tumor effect of cycloparamide in vertebrates are related to the hedgehogsignaling pathway mediated by SHH gene. When the pathway is over inhibited, it will affect embryonic development and cause fetal malformation; When it is over activated, it will affect the process of tumor formation. Cycloparamide can inhibit the intracellular signal transduction of SMO and further inhibit the transcription and expression of tumor and shadow by binding to the seven helix cluster region of SMO.
Cyclopamine It is a potential anti-tumor drug, but it has certain toxic and side effects on normal tissues. Therefore, it is necessary to improve its tumor selectivity. Cyclobalamine and its derivatives were prepared from different sources by means of chemical synthesis and separation of natural products. The structure-activity relationship was further improved through in vivo and in vitro activity studies, and ideal candidate compounds with antitumor activity were screened out. At the same time, it should be the focus of current research in this field to carry out animal in vivo trials and even clinical trials as soon as possible, so as to obtain a complete evaluation of the toxicology, pharmacokinetics and pharmacodynamics of cymbalamine and its analogues. With the further research on cyclophosphamide and its analogues, we believe that such drugs will bring new hope to cancer patients.