Approaches for the Synthesis of Functionalized Cryptophycins

Abstract

The first syntheses of bioactive cryptophycins functionalized at unit D were accomplished in a one-pot Staudinger reduction/cyclization step. An azido precursor for the lower part of the backbone was introduced to minimize protective group chemistry and enable a very convenient synthesis of cryptophycin-52 and unit D cryptophycin analogues containing an ester or a free carboxylic acid for bioconjugations. Both new cryptophycin derivatives show high biological activity in cytotoxicity assays.

Isolation of non-cytotoxic crotepoxide from the root bark of Croton macrostachyus and the reassignment of its structure

“…Cytotoxic activity of the isolated compounds was done as described [9]. Briefly the KB-3-1 cells were cultivated as a monolayer in a DMEM (Dulbecco's Modified Eagel Medium) with glucose (4.5 g/L), L-glutamine, sodium pyruvate and phenol red, supplemented with 10% (KB-3-1) foetal bovine serum (FBS).…”

Dialiumoside, an Olean-18-ene Triterpenoid from Dialium excelsum

“…P-glycoprotein (P-gp) represents an ATP-dependent efflux system that actively transports structurally diverse xenobiotics to the outside of the cell. For both cell lines, the reduction of resazurin to resorufin was used as readout [18]. Dialiumoside (1) and luteolin (13) All other tested compounds were inactive against both cell lines.…”

“…Cytotoxic activity screening of the isolates was done as described in previous reports [18]. The KB-3-1 and KB-V1 cells were cultivated as a monolayer in DMEM (Dulbecco's modified Eagle medium) with glucose (4.5 g L −1 ), L-glutamine, sodium pyruvate and phenol red, supplemented with 10 % (KB-3-1) and 15 % (KB-V1) foetal bovine serum (FBS).…”

Cytotoxic flavonoids from Erythrina caffra Thunb

“…The method used for this cytotoxicity test was the cell-based resazurin cytotoxicity assay with fluorescence readout. Human cervix carcinoma KB-3-1 cells were used and the reduction of the resazurin to resorufin was used as read out [23]. Of the seventeen pure isolates, compounds 3, 5, 6, 8, 9, 10, 11, 12, 13, 15 and 16 were found to be active against the human cervix carcinoma KB-3-1 cells with IC 50 values in the micromolar range (Table 1).…”

“…Cytotoxic activity of the isolates and crude extracts was done as described [23]. Briefly the KB-3-1 cells were cultivated as a monolayer in a DMEM (Dulbecco's Modified Eagel Medium) with glucose (4.5 g/L), L-glutamine, sodium pyruvate and phenol red, supplemented with 10% (KB-3-1) foetal bovine serum (FBS).…”