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

摘要

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 298K for THA, pK_1=4.82±0.05 (phenolic -OH at C_2) and particularly pK_2=9.22±0.05 (phenolic -OH at C_1 and C _4) closely resemble those of the anthracyclines. THA undergoes a single step two-electron reduction in aqueous media (pH 7.36) having E 1/2=-0.69V and two successive single-electron reduction in DMF having E_(1/2) values -0.70V and -1.06V, respectively. CV data showed quasi-reversible nature of THA in aqueous media. E_(1/2) 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)× 10~4M~(-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 IC_(50) value of 33.8μM. 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.