New tacrine dimers with antioxidant linkers as dual drugs: Anti-Alzheimer's and antiproliferative agents

Multifunctional properties of novel tacrine congeners: cholinesterase inhibition and cytotoxic activity

“…Roldán‐Peña et al () described a series of tacrine‐based homo‐ and heterodimers with antioxidant linkers and suggested their potential use as new anti‐Alzheimer's and antiproliferative agents. The synthesized compounds can be divided into three groups.…”

“…Preparation of tacrine‐derived selenoureas 26–28 , and diselenides 29 and 30 and disulfides 31 and 32 (Roldán‐Peña et al, )…”

“…In an effort to develop drugs that could treat both AD and cancer simultaneously, Roldán‐Peña et al () developed a large series of tacrine‐based homo‐ and heterodimers incorporating antioxidant chains. Experiments were also performed to assess the new agents' inhibition effect on recombinant h AChE was performed and the activity was compared to two structurally related tacrine derivatives, bis(7)tacrine 34 (IC 50 for h AChE = 0.81 n m ) (Bolognesi et al, ) and cystamine–tacrine derivative 35 (IC 50 for h AChE = 5.04 n m ) (Munoz‐Torrero & Camps, ) (Figure ).…”

“…Roldán‐Peña et al also revealed the importance of keeping a protonable amino group under physiological conditions on tacrine residue; using such an approach with 6‐(phenylseleno)hexyl derivative 25 led to a remarkable increase in activity for the compound, a level approximately 440 times higher than that of the non‐pronated Se‐phenylacetamide 24 . The protonated compound 25 can mimic the iminium cation of the natural enzymatic substrate, and thus effectively bind to the catalytic site; such a situation is not possible in the case of compound 24 due to the absence of a basic group (Roldán‐Peña et al, ).…”

“…Roldán‐Peña et al () designed a series of tacrine‐based dimers that incorporate tethers of selenoureido derivatives ( 26–28 ) or chalcogenide derivatives ( 29–32 ). The studied compounds exhibited excellent in vitro antiproliferative activities against human tumor cell lines A549 (non‐small cell lung), HBL‐100 (breast), HeLa (cervix), SW1573 (non‐small cell lung), T‐47D (breast) and WiDr (colon), with GI 50 values within the submicromolar range.…”