Interactions of cryptolepine and neocryptolepine with unusual DNA structures

Abstract

1 These authors contributed equally to this work. AbstractCryptolepine, the main alkaloid present in the roots of Cryptolepis sanguinolenta, presents a large spectrum of biological properties. It has been reported to behave like a DNA intercalator with a preference for GC-rich sequences. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of cryptolepine and neocryptolepine for DNA structures among duplexes, triplexes, quadruplexes and single strands. Our data confirm that cryptolepine and neocryptolepine prefer GC over AT-rich duplex sequences, but also recognize triplex and quadruplex structures. These compounds are weak telomerase inhibitors and exhibit a significant preference for triplexes over quadruplexes or duplexes.

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

“…This is a recurrent observation for a number of quadruplex ligands: it has been relatively difficult to dissociate triplex and quadruplex affinity. Most of the quadruplex ligands exhibit similar and sometimes higher affinity for antiparallel triplexes [24,41]. Another potential problem, when in vivo applications are contemplated, comes from the fact that very few quadruplex ligands distinguish between the various classes of G-quadruplexes (intra-or intermolecular, parallel or antiparallel).…”

“…Several reviews concerning telomerase inhibitors in general or quadruplex-based telomerase inhibitors have been published in the last few years [16][17][18][19][20][21][22][23]. The recent discovery of natural compounds such as cryptolepine [24] and telomestatin [25,26] or of synthetic pentacyclic acridines (such as RHPS4) [27] that interact with G-quartets led us to test the binding of ascididemin and meridine to G-quadruplexes.…”

“…We have adapted this test to accommodate a different set of nucleic acid structures [24,34]. Briefly, a buffer consisting of 15 mM sodium cacodylate (pH 6.5), 10 mM MgCl 2 , and 185 mM NaCl was used for all experiments.…”

“…A panel of 19 different nucleic acids structures were used. They have been described in details elsewhere [24]. All 19 dialysis units were then placed in the beaker containing the dialysate solution.…”

Synthesis and Antiproliferative Activity of Novel Neocryptolepine-Hydrazides Hybrids

“…1) which are naturally occurred as indoloquinoline alkaloids isolated from the shrub Cryptolepis sanguinolenta, that is growing in west Africa, used for treatment of endemic disease such as malaria fever and various disorder of the body are important due to their wide spectrum of biological properties (Cimanga et al, 1996;El Sayed et al, 2009;Jonckers et al, 2002;Lavrado et al, 2010;Lu et al, 2013;Prakash et al, 2011;Mei et al, 2013;Wang et al, 2013Xu and Pieters 2013;Emam et al, 2015;Okada et al, 2016;Larghi et al, 2015;Peng et al, 2012) However, a direct comparison of the cytotoxicity of cryptolepine and neocryptolepine demonstrated that the latter was much less cytotoxic and high affinity towards DNA. (Bailly et al, 2000;Guittat et al, 2003).…”