Supramolecular complex binding to G-quadruplex DNA: Berberine encapsulated by a planar side arm–tethered β-cyclodextrin

Abstract

G-quadruplex-binders have the plausible potential to act as anticancer agents. Herein, the mode of binding of a synthesized fluorenyl derivative of β-cyclodextrin with a duplex and G-quadrulex DNAs has been investigated. Moreover, the loading of the well-known G-quadruplex binder, berberine, in the β-cyclodextrin derivative using 2-dimensional rotating-frame Overhauser effect spectroscopy is studied. The intensity of proton NMR signals is weakened on the β-cyclodextrin derivative's interaction with the quadruplexes. Binding constants are reported for each binding of the ligands to calf thymus DNA, kit22, telo24, and myc22 employing fluorescence spectroscopy. A general trend of fluorescence response (quenching) on the β-cyclodextrin derivative to the DNAs is modified when the berberine molecule is loaded in the host structure. Despite berberine binds to the macromolecular target strongly, its host-guest association with the cavity of β-cyclodextrin diminishes the binding strength. A significant difference between the binding strengths of the ligands with duplex and quadruplex structures is observed. Communicated by Ramaswamy H. Sarma.

Non-canonical DNA structures: Diversity and disease association

“…Exploring various G-quadruplex stabilizing drugs have been proven significant for the development of anticancer drugs. For example, ligands like berberrubine ( Saha et al, 2019 ), berberine ( Suganthi et al, 2018 ), quercetin ( Vinnarasi et al, 2019 ), and telomestatin ( Kim et al, 2003 ) have been documented as DNA G-quadruplex stabilizing drugs possessing anticancer properties.…”

“…Frontiers in Genetics frontiersin.org example, ligands like berberrubine (Saha et al, 2019), berberine (Suganthi et al, 2018), quercetin (Vinnarasi et al, 2019), and telomestatin have been documented as DNA G-quadruplex stabilizing drugs possessing anticancer properties. Moreover, the gene therapy of various diseases has also been studied by targeting G-quadruplexes by compounds like ranitidine chloride and benzophenanthridine derivative.…”

Effects of Berberine on Liver Cancer

“…Table 4 shows several formulation techniques particularly designed for tackling the limitations (poor intestinal absorption, poor pharmacokinetic, or poor bioavailability) associated with BBR administration, thereby promoting its anti-cancer efficacy. 29–45 These involve nanocarriers or nanoparticles of different surface charges and size with few targeting subcellular organelles like mitochondria. For instance, the experimental studies carried out by Khan et al, demonstrated a 14-fold elevation in the half-life of BBR in a mice model through poly (lactic-co-glycolic acid) (PLGA) nanoparticle BBR carriers, while the charged vitamin E-based amphiphilic mixed micellar vehicles provided a 30-fold enhancement in BBR pharmacokinetics.…”

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

“…It is worth reiterating that poor intestinal absorption, extensive efflux by the action of P-gc and extensive degradation account to the rather poor bioavailability/pharmacokinetics profile of berberine. The various formulation approaches specifically designed to tackle this problem and improve berberine's anticancer efficacy are shown in Table 2 [106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123]. These include nanoparticles of various sizes and surface charges with some specifically targeting subcellular organelles, such as the mitochondria.…”