Cyclic voltammetric studies of 1,2,4‐trihydroxy‐9,10‐anthraquinone, its interaction with calf thymus DNA and anti‐leukemic activity on MOLT‐4 cell lines: a comparison with anthracycline anticancer drugs

Abstract

Anthracycline drugs show anticancer activity, an ability to inhibit DNA replication and RNA transcription but are costly. This study attempts to see if cheaper hydroxy‐9,10‐anthraquinones (1,2,4‐trihydroxy‐9,10‐anthraquinone) that structurally resemble anthracyclines mimic its biological interactions and whether it can be a suitable substitute. Proton dissociation at 298 K for THA, pK1 = 4.82 ± 0.05 (phenolic OH at C2) and particularly pK2 = 9.22 ± 0.05 (phenolic OH at C1 and C4) closely resemble those of the anthracyclines. THA undergoes a single step two‐electron reduction in aqueous media (pH 7.36) having E1/2 = −0.69 V and two successive single‐electron reduction in DMF having E1/2 values −0.70 V and −1.06 V, respectively. CV data showed quasi‐reversible nature of THA in aqueous media. E1/2 values of THA were comparable to anthracycline drugs suggesting similarity in redox behavior. Binding studies of THA to ct DNA using UV–Vis and fluorescence spectroscopy were analyzed. Intrinsic binding constant and site size of interaction were (4.80 ± 0.2) × 104 M−1 and (5.96 ± 0.3) bases, respectively. THA, approximately three to five times weaker in binding ct DNA than anthracycline anticancer drugs suggests a role for sugar moieties present in anthracyclines. Anti‐leukemic activity studies of THA on cultured MOLT‐4 cell lines were performed and apoptosis measured by MTT assay. Result indicates THA to be a potent inducer of apoptosis in MOLT‐4 cell line having an IC50 value of 33.8 µM. THA therefore possesses anti‐leukemic activity that is comparable to anthracyclines on P388 leukemia and the study reveals that 1,2,4‐trihydroxy‐9,10‐anthraquinone to be a suitable substitute to the costlier anthracyclines. Copyright © 2011 John Wiley & Sons, Ltd.

Interaction of Calf Thymus DNA with the Ni(II) Complex of Sodium 1,4-Dihydroxy-9,10-Anthraquinone-2-Sulphonate: A Novel Method of Analysis Using Cyclic Voltammetry

“…To do so, the following compound-DNA equilibrium was considered [32,[34][35][36][37][52][53][54][55]:…”

“…As there is no interference from the DNA bound form the cathodic peak current (I pc ) is therefore linearly proportional to the concentration of Na 2 [Ni(NaLH) 2 Cl 2 ]·2H 2 O (1) [40]. Using this linear relationship between cathodic peak current and concentration of the compound and applying the same analogy that one applies for absorption and fluorescence methods [32,[34][35][36][37][52][53][54][55] the following parameters can be defined. ΔI = (I 0 pc − I pc ) = change in cathodic peak current (I pc ) of Na 2 [Ni(NaLH) 2 Cl 2 ]·2H 2 O at −515 mV (versus Ag/AgCl, satd.…”

“…In recent studies [32,[34][35][36][37], we were successful in showing that 1,4-dihydroxy-9,10-anthraquinone, 1,2,4-trihydroxy-9,10-anthraquinone, NaLH 2 and its Cu(II) complex interact with calf thymus DNA (CT DNA), and that the binding parameters evaluated [32] were close to those reported for the anthracycline drugs [38]. Encouraged by these findings, we decided to extend the study to an Ni(II)-NaLH 2 complex because of a difference in electronic constitution with Cu(II).…”

Exploration of Electrochemical Intermediates of the Anticancer Drug Doxorubicin Hydrochloride Using Cyclic Voltammetry and Simulation Studies with an Evaluation for Its Interaction with DNA

“…Since there was no interference from doxorubicin hydrochloride-DNA adduct [34], the cathodic peak current ( pc ) was linearly proportional to the concentration of free, that is, nonbound, doxorubicin hydrochloride (see (1)). Using this linear relationship between cathodic peak current and concentration of doxorubicin hydrochloride and applying the same analogy one applies for absorption and fluorescence, the following parameters were defined [36][37][38][39]. Δ = ( pc 0 − pc ) = change in cathodic peak current ( pc ) of doxorubicin hydrochloride at −690 mV (versus Ag/AgCl, saturated KCl) upon each addition of CT DNA for each point of the titration.…”

“…Results of DNA titration using cyclic voltammetry were analyzed by the method of nonlinear fitting [25,26]. To do so, the following compound-DNA equilibrium was considered [36][37][38][39]:…”