Synthesis and Anticancer Activity of 4β-Triazole-podophyllotoxin Glycosides

Abstract

A series of novel 4β-triazole-podophyllotoxin glycosides were synthesized by utilizing the Click reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assay shows that most of these compounds show weak cytotoxicity. It was observed that compound 16 shows the highest activity with IC50 values ranging from 2.85 to 7.28 μM, which is more potent than the control drugs etoposide and cisplatin against four of five cancer cell lines tested. Compound 16 is characterized with an α-d-galactosyl residue directly linked to the triazole ring and a 4′-OH group on the E ring of the podophyllotoxin scaffold. HPLC investigation of representative compound indicates that incorporation of a sugar moiety seems to improve the chemical stability of the podophyllotoxin scaffold.

Synthesis and Cytotoxicities of Novel Podophyllotoxin Xyloside Derivatives

“…Previously, we had reported the cytotoxic activity of 4β-triazole-podophyllotoxin xylosides (all having IC 50 >40 µM against 5 cancer cell lines). 17 However, we have found in this study that per-butyrylation of the xylose residue leads to increased cytotoxic activity. As compounds 10 and 11 do not show in vitro efficacy, we have calculated the ClogP and polar surface area (PSA) values of compounds 8 to 11 by Sybyl, 18 and the data are shown in Table 2.…”

“…Previously, we had reported the cytotoxic activity of 4β-triazole-podophyllotoxin xylosides (all having IC 50 >40 µM against 5 cancer cell lines). 17 However, we have found in this study that per-butyrylation of the xylose residue leads to increased cytotoxic activity.…”

Synthesis and Cytotoxic Activity of New 1,3,4-Thiadiazole Thioglycosides and 1,2,3-Triazolyl-1,3,4-Thiadiazole N-glycosides

“…A number of nucleoside analogues such as Cytarabine, Azacitidine, Capecitabine, Floxuridine, and Decitabine are indeed ratified with antitumor activity [26]. Figure 1 displays a number of reported highly active 1,3,4-thiadiazole and triazole glycosides ( I , III , and IV ) and the triazole–thiadiazole hybrid II against different cancer cells [7,8,9,27,28]. Such significances and our interest in synthesizing new active glycosyl heterocycles [29,30,31,32,33], enhanced our foresight that the 1,3,4-thiazoles and triazoles motif hybrid compounds and their sugar linked products could be useful systems for designing novel cytotoxic agents.…”

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

“…Therefore, apart from macromolecular targeted drug development, investigation includes the existing anticancer drug candidates in parallel being tested with the purpose to develop more potent targeted drug molecule. In this context, Hu and co-workers designed a class of 4β-triazolyl-podophyllotoxin glycohybrids via regioselective bridging of clickable terminal alkynes with the azide of podophyllotoxin analogues . The developed analogues were subjected to anticancer evaluation against five human cancer cell lines.…”

“…The resulting molecules were investigated for antibacterial activity against drug-sensitive and drug-resistant strains and demonstrated excellent broad-spectrum activity with improved sensitivity for resistant bacterial strains. Compounds 1149a – c displayed potent activity against sensitive bacterial strains S. aureus and B. subtilis ; on the other hand, compounds 1139d and 1139e (Figure ) showed promising activity for S. pneumoniae . Additional MBC investigation revealed that the compounds 1149a – e were also potent bacteriostatic agents.…”