Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

Abstract

Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC50: 1.41–1.76 μM) and 14e (IC50: 1.72–2.01 μM) showed superior cytotoxic activity compared with etoposide (IC50: 2.03– >20μM), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4′-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin’s 4β position can significantly improve cytotoxic activity.

Toward synthesis of third-generation spin-labeled podophyllotoxin derivatives using isocyanide multicomponent reactions

“…Remarkably, these compounds retained similar levels of cytotoxicity against the drug resistant KBvin and KB tumor cell lines, while 2 lost its activity completely (IC 50 > 20 vs 3.88 µM). This result agrees with our prior observation that C4-amino substitution of epipodophyllotoxin is good for overcoming drug-resistance [34–36]. Among the tested compounds, compounds 12e and 12h showed superior activity with IC 50 values of 0.60–1.46 µM compared to those of 2 (IC 50 2.03–3.88 µM) against A549, DU-145, and KB tumor cell lines.…”

Diterpenoids from the stems of Tripterygium hypoglaucum (Celastraceae) and cytotoxic evaluation

“…C4.1.4 (CHCl 3 -MeOH 7:3, 135 mg) was applied on a MPLC Lichroprep RP-18 column (20 mm  150 mm, 3 mL/min, MeOH-H 2 O 3:2, 4:1, each 500 mL) to give 6 (10 mg, 35 min) and 10 (2 mg, 63 min). Tables 1 and 2) (Zhang et al, 2014) Cytotoxicity was determined by the sulforhodamine B (SRB) colorimetric assay as previously described. The panel of five cell lines included human lung carcinoma (A549), epidermoid carcinoma of the nasopharynx (KB), P-gp-expressing epidermoid carcinoma of the nasopharynx (KBvin), prostate cacer (DU145), and triple-negative breast cancer (MDA-MB-231).…”

New abietane-type diterpene glycosides from the roots ofTripterygium wilfordii

“…Cytotoxicity was determined by the sulforhodamine B (SRB) colorimetric assay according to our protocol [18]. Briefly were seeded in 96-well plates filled with RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) containing various concentrations of compounds, and incubated for 72 h. At the end of the exposure period, the attached cells were fixed with cold 50% trichloroacetic acid for 30 min followed by staining with 0.04% SRB (Sigma Chemical Co.) for 30 min.…”