13580-38-6Relevant articles and documents
Synthesis and anticancer activity of dimeric podophyllotoxin derivatives
Zi, Cheng-Ting,Yang, Liu,Xu, Feng-Qing,Dong, Fa-Wu,Yang, Dan,Li, Yan,Zhou, Jun,Hu, Jiang-Miao,Ding, Zhong-Tao,Jiang, Zi-Hua
, p. 3393 - 3406 (2018)
Background: Podophyllotoxin is a potent cytotoxic agent and serves as a useful lead compound for the development of antitumor drugs. Several podophyllotoxin-derived antitumor agents, including etoposide, are currently in clinical use; however, their therapeutic efficacy is often limited due to side effects and the development of resistance by cancer cells. Previous studies have shown that 4Β-1,2,3-triazole derivatives of podophyllotoxin exhibit more potent anticancer activity and better binding to topoisomerase-II than etoposide. The effect of dimerization of such derivatives on the anticancer activity has not been studied. Methods: Two moieties of podophyllotoxin were linked at the C-4 position via 1,2,3-triazole rings to give a series of novel dimeric podophyllotoxin derivatives. 4Β-Azido-substituted podophyllotoxin derivatives (23 and 24) were coupled with various dipropargyl functionalized linkers by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to provide dimeric products in very good yield. The in vitro anticancer activity of the synthesized compounds was evaluated by MTT assay against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480). The normal BEAS-2B (lung) cell line was also included for study in order to evaluate the cancer selectivity of the most active compound as compared with normal cells. Results: A group of 16 dimeric podophyllotoxin derivatives with different linkers were synthesized and structurally characterized. Most compounds do not show significant cytotoxicity (IC50 > 40 mM) against all five cancer cell lines. However, one compound (29) which bears a perbutyrylated glucose residue on the glycerol linker is highly potent against all five cancer cell lines tested, with IC50 values ranging from 0.43 to 3.50 μM. This compound (29) also shows good selectivity towards cancer cell lines as compared with the normal BEAS-2B (lung) cell line, showing selectivity indexes from 4.4 to 35.7. Conclusion: The anticancer activity of dimeric podophyllotoxin derivatives is generally speaking not improved as compared to their monomeric counterparts, and the potency of these dimeric derivatives can be largely affected by the nature of the linker between the two moieties. Among the synthesized derivatives, compound 29 is significantly more cytotoxic and selective towards cancer cells than etoposide and cisplatin, which are currently in clinical use. Compound 29 is a promising anticancer drug and needs further studies.
Design and Synthesis of Galactose-Biotin Lipid Materials for Liposomes to Promote the Hepatoma Cell–Targeting Effect
Ding, Ruihua,Li, Zhenjie,Wang, Jianyi,Zhu, Xueyan,Zhao, Zhuang,Wang, Mian
, p. 3074 - 3081 (2019/05/07)
A series of novel low-toxic hepatoma cell–targeting lipid materials were designed and synthesized, in which monogalactose, digalactose, and galactose-biotin were used as targeting moieties and hydrophilic heads while stearate was used as hydrophobic tail (Mono-Gal-ST, Di-Gal-ST, and Gal-Biotin-ST). The corresponding galactose-biotin-modified liposomes (Mono-Gal-LPs, Di-Gal-LPs, and Gal-Biotin-LPs) and conventional liposomes (LPs) were prepared. These galactose-biotin-modified liposomes can distinguish hepatoma cells from other tissue cells owing to the recognition of asialoglycoprotein receptor by galactose group. Moreover, the ability of liposomes to distinguish hepatoma cells from normal hepatocytes follows a trend of LPs Mono-Gal-LPs Di-Gal-LPs Gal-Biotin-LPs, which is attributed to the cluster glycoside effect and the synergistic effect of galactose and biotin. In addition, the endocytosis of these galactose-biotin-modified liposomes were competitively inhibited by galactose, further confirming these liposomes entered hepatoma cells via asialoglycoprotein receptor–mediated pathway.
HIV INTEGRASE INHIBITORS
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Page/Page column 85, (2010/04/28)
Compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: (I), wherein X1, X2, Y, R1A, R1B, R2 and R3 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset or progression of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se (or as hydrates or solvates thereof) or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
