Design, synthesis and biological evaluation of novel podophyllotoxin derivatives bearing 4β-disulfide/trisulfide bond as cytotoxic agents

Abstract

A novel series of podophyllotoxin derivatives bearing 4β-disulfide/trisulfide were designed, synthesized and biologically evaluated for their cytotoxic activities against KB cells and KB/VCR cells.

Glycosyl disulfides: importance, synthesis and application to chemical and biological systems

“…4) were evaluated for their cytotoxicity against human cancer cell lines, including KB (Mouth Epidermal Carcinoma Cells) and KB/VCR (Vincristine-resistant Mouth Epidermal Carcinoma Cells). 103 The anticancer drug etoposide (Fig. 4) is a podophyllotoxin analogue widely used for treatment of numerous solid tumours, 104 but like many cancer chemotherapeutics, is known to cause several undesirable side effects and drug-resistance problems in the clinic.…”

One pot synthesis ofthio-glycosidesviaaziridine opening reactions

“…† Briefly, the 1-Sacetyl derivatives of mannose (Man), rhamnose (Rha), glucose (Glc), galactose (Gal) and lactose (Lac) (Scheme 2, 1 and 6-9) were obtained by acid catalysed acetylation of the free sugar, followed by reaction with thioacetic acid (AcSH) under TMSOTf or BF 3 catalysis (two step, one pot). 20,21 The 1-S-acetyl derivatives of sialic acid (Neu5Ac) and N-acetylglucosamine (GlcNAc) 22 (Scheme 2, 10-11) were synthesized by reaction of AcSK with the corresponding peracetylated anomeric chloride, generated in situ by reaction of the free sugar with AcCl. In most cases, the peracetylated glycosyl thio-acetates were obtained as single isomers and, when not, the two isomers were chromatographically separated (see ESI †).…”

“…23 The peracetylated glycosyl thio-acetates 1-9 were obtained as described in ref. 20,21 The Neu5Ac and GlcNAc derivatives 10 and 11 were synthesized according to ref. 22.…”

Synthesis of Unsymmetric Trisulfides from 9-Fluorenylmethyl Disulfides

“…Moreover, natural product- and protein-derived trisulfides are also known. 8–10 Figure 1 shows two such examples. Trisulfides have decent stability in aqueous solutions and biological systems.…”