Boehmeriasin A as new lead compound for the inhibition of topoisomerases and SIRT2

Abstract

Two synthetic approaches to boehmeriasin A are described. A gram scale racemic preparation is accompanied by an efficient preparation of both the pure enantiomers using the conformationally stable 2-piperidin-2-yl acetaldehyde as starting material. The anti-proliferative activity in three cancer cell lines (CEM, HeLa and L1210) and two endothelial cell lines (HMEC-1, BAEC) indicates promising activity at the nanomolar range. Topoisomerases and SIRT2 are identified as biological targets and the experimental data has been supported by docking studies.

Stereodivergent Diversity‐Oriented Synthesis: Exploiting the Versatility of 2‐Piperidine Ethanol

“…Considering our interest in natural products, we took advantage of this approach to synthesize some alkaloids (aloperine, [6] different sedum alkaloids, [7] dumetorine, epidihydropinidine, coniine, [8] boehmeriasin A [9] ) but also some synthetic derivatives, such as polyheterocyclic derivatives [10] and hybrid compounds ( Figure 1). Among the methods useful for the gen- cemic form, contains two handles -the piperidine nitrogen and the hydroxyl group -which can be easily further functionalized, increasing in this way the structural complexity.…”

Use of chiral-pool approach into epi-thieno analogues of the scarce bioactive phenanthroquinolizidine alkaloids

“…In the light of these results, numerous efforts were undertaken to carry out quantitative structureeactivity relationship (QSAR) studies (Scheme 1). 6 Out of such considerations, the synthesis of these natural products and derivatives has been an appealing area of research. 5 While these studies were based essentially on Cryptopleurine (1) as the alkaloid model, the more recent Boehmeriasin-A (4) based compounds have shown in in vitro study anti-proliferative activity in three cancer cell lines (CEM, HeLa, and L1210) and in two endothelial cell lines (HMEC-1, BAEC) at concentration near the nanomolar range.…”

“…The results of certain phenanthroquinolizidine derivatives show inhibitory activity in three human cancer cell lines with appreciable IC 50 (104e130 nM), 2 the potential to treat coronavirus infection, 3 good to excellent in vivo antiviral activity against tobacco mosaic virus (TMV) 4 and anti-proliferative and selective antitumor properties. The ring closure of the central ring D proceeded then by FriedeleCrafts cyclization as pioneered by Rapoport et al, 6,7 the Parham-type cycloacylation 8 and intramolecular aldol-type condensation. Interestingly, during these studies, topoisomerases and SIRT2 were identified to be biological targets of these structures.…”

Novel benzoquinoline derivatives via unpredicted condensation of ethyl propiolate and naphthylamines: Synthesis and topoisomerase inhibition activity

“…34,36,37 The poisoning effect can be experimentally demonstrated by a cleavable complex assay which allows the detection of the topoisomerase II-dependent formation of linear from supercoiled DNA. 38 Figure 4 shows the results obtained from the cleavage complex assay carried out in the presence of two concentrations of 7a, i.e. 100 and 200 μM, and of m-AMSA at 8 μM, as reference.…”