Spectroscopic, viscometric and computational binding study of 1 and 2 substituted anthraquinone analogs to be potential anti-cancer agents

Mitoxantrone is a well-known anthraquinone class of anti-cancer drug used against a variety of cancers. To examine the positional effect of substituent groups on the bioactivities of biologically important anthraquinone class of compounds, two analogs (1PAQ and 2PAQ) having 1-oxo-3-phenyl-2(benzosulfonamide)-propylamide attached at either 1 or 2 position of the 9,10-anthraquinone ring are synthesized. The synthesized analogs are characterized using FT-IR, 1H NMR, ESI-MS, HR-MS, C-13 NMR techniques. These synthesized analogs exhibit pharmacological properties comparable to that of standard drug Mitoxantrone. Cytotoxicity of 1-substituted (1PAQ) and 2-substituted (2PAQ) anthraquinone analogs were evaluated against Hep2C, PC-3 and MCF-7 cancer cell lines. Analog substituted at position 1 was found to be more active against Hep2C and MCF-7 cell lines than 2-substituted anthraquinone analog. Absorption, emission, electrochemical and viscometric study of the binding of 1PAQ and 2PAQ, as well as standard drug Mitoxantrone with ct-DNA has also been carried out. Partial intercalation mode followed by external binding with the binding constant (K-b) in the range similar to 10(4)-10(6) M-1 has been observed. The change in position and intensity of bands in FT-IR spectra of complexes also indicate the binding of molecules with base pairs of ct-DNA, although the interactions are weak with the DNA backbone. Experimental results have been supported by a docking study. Using the HF/6-31 G (d, p) method, the total energy, HOMO-LUMO energy gap, dipole moment and other parameters like chemical hardness, chemical softness and electronegativity of the molecules have been calculated to study the electronic distribution of charge over the molecules. The study supports the spectrophotometric titrations. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Mitoxantrone, a well-known anthraquinone anti-cancer drug, has analogs 1PAQ and 2PAQ synthesized for studying their bioactivities. The analogs showed pharmacological properties comparable to Mitoxantrone, with 1-substituted analog exhibiting higher activity against Hep2C and MCF-7 cell lines. Experimental results were supported by a docking study.