Chemoinduction of cytotoxic selectivity in Podophyllotoxin-related lignans

The search for plants with anticancer activity: Pitfalls at the early stages

“…Many different normal cell lines have been used for comparison with the results from cancer cell lines. They are generally immortalized cell lines, primary fibroblasts, different types of animal cell lines or human peripheral blood mononuclear cells (Atjanasuppat et al, 2009;Barros et al, 2011;Castro et al, 2003;Cordero et al, 2009;Houghton et al, 2007b;Kpoviessi et al, 2014;Sawada et al, 2005;Seal and Mukherjee, 2002;Wang et al, 2002). In the next section, we offer arguments, supported by experimental data, that the inclusion of such "normal" cells in inhibitory assays is unnecessary and in fact may lead to false conclusions as to the "selectivity" of the extract or compound under study.…”

Antitumor activity of a novel dual functional podophyllotoxin derivative involved PI3K/AKT/mTOR pathway

“…Etoposide is a podophyllotoxin (Ptox) derivative isolated from the Podophyllum species [3], but severe side-effects and multidrug resistance (MDR) often result in treatment failure. To overcome the current limitations, numerous approaches have been made to modify the structure of Ptox [4], including esterification and amination at position 4 to produce 4′-demethylepipodophyllotoxin (DMEP) [5], C-S bond modified aromatic heterocyclic podophyllum derivatives [6], acyl thiourea derivatives of epipodophyllotoxin [7], pyridine acid ester derivatives of Ptox [8], halogen-containing aniline Ptox derivatives [9], and combination of 5-Fu with DMEP derivatives [10]. These modifications were achieved using a molecular hybridization strategy [11,12], and some of the derivatives displayed much better cytotoxic activity than etoposide at the cellular level.…”

Design and synthesis of 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives as novel anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase

“…1), which creates challenges for SAR (structure-activity relationship) studies.Research efforts to develop new analogues with simpler structures are ongoing ot identify the critical substructures for desired biological activity, and almost all rings (ring A to E) and positions on the cyclolignan skeleton have been modified. 8 Importantly, elimination of the stereogenic centers at C-2 and C-3 removes the possibility of epimerization at C-2. Epimerization of the natural lignan has plagued its clinical development, because the rapidly formed in vivo cis -lactone metabolite is inactive.…”