Natural isoquinoline alkaloids: binding aspects to functional proteins, serum albumins, hemoglobin, and lysozyme

Abstract

The putative anticancer alkaloids berberine, palmatine, jatrorrhizine, and sanguinarine are known to bind to nucleic acids. To develop them as potential drugs for therapeutic use, their binding affinity to functional proteins and mode of transport in the circulatory system need to be clearly understood. Towards this, many studies on their binding aspects to proteins have been reported and a considerable amount of data, mostly of biophysical nature, exists in the literature. The importance of these natural isoquinoline alkaloids and the recent literature on their interaction phenomena with functional proteins, serum albumins, hemoglobin, and lysozyme are presented in this review.

Keywords: Hemoglobin; Interaction; Isoquinoline alkaloids; Lysozyme; Serum albumins.

Fig. 1

Chemical structures of: a isoquinoline moiety, b benzylisoquinoline moiety, c berberine, d palmatine, e jatrorrhizine, f sanguinarine (iminium form), and g sanguinarine (alkanolamine form)

Fig. 2

Three-dimensional structure of: a BSA and b HSA

Fig. 3

Emission spectra of HSA in the presence of various concentrations of berberine. The inset shows the Stern–Volmer plot. c (HSA) = 1.0 × 10⁻⁵ M⁻¹; c (berberine)/(10⁻⁵ M⁻¹); curves A–M, from 0.0 to 2.4 at increments of 0.20; curve N (dashed line) shows the emission spectrum of berberine only (T = 298 K, λ _ex = 295 nm) [reprinted from Hu et al. (2009) with permission from the American Chemical Society)]

Fig. 4

ITC profiles for the binding of berberine to BSA and HSA at T = 298.15 K. The upper panels represent the plot of enthalpy against time, representing the raw data for the sequential injection of a BSA (0.50 mM) and b HSA (0.60 mM) into berberine (0.05 mM) and dilution of the proteins into buffer (curves at the top are offset for clarity). The lower panels show the integrated heat data after correction of heat of dilution against the molar ratio of [Protein]/[Alkaloid]. The data points (closed squares) were fitted to a one-site model and the solid lines represent the best-fit results [reprinted from the Ph.D. thesis of A.Y. Khan (2013)]

Fig. 5

Location of jatrorrhizine molecule on the HSA subdomain IIIA (site II). The structural details of the interaction between jatrorrhizine and HSA obtained by the molecular modeling method is shown in the expanded region. Jatrorrhizine molecule is shown as a cylinder model (C, gray; O, red; N, blue; H, turquoise) [reprinted from Mi et al. (2014) with permission from Elsevier B.V.]

Fig. 6

Three-dimensional structure of Hb

Fig. 7

a The intrinsic circular dichroism (far UV CD) spectral changes of Hb (1 μM) on interaction with 0, 2.23, 4.46, 6.66, 8.86, 11.05, 13.23, and 15.39 μM of palmatine (curves 1–8). b The Soret band CD spectral changes of Hb (5 μM) on interaction with 0, 2.67, 5.35, 8.02, 10.67, 13.33, 15.98, and 18.63 μM of palmatine (curves 1–8) [reprinted from Hazra et al. (2013) with permission from the Royal Society of Chemistry]

Fig. 8

Plot of ΔG ⁰ (filled symbols) and ΔH ⁰ (open symbols) versus TΔS ⁰ for the binding of berberine (squares) and palmatine (triangles) with Hb [reprinted from Hazra et al. (2013) with permission from the Royal Society of Chemistry]

Fig. 9

Three-dimensional representation of Lyz

Fig. 10

Hydrogen-bonding network and positioning of cleavage point residues (Glu-35–Asp-52) with docked sanguinarine alkanolamine (a) and iminium forms (b). The black dotted lines represent H bonds; important residues are colored purple [reprinted from Jash et al. (2014) with permission from the American Chemical Society]