Synthesis, cytotoxic evaluation and ct-DNA binding of series of 1,4-disubstituted anthraquinone-sulfonamide conjugates

A series of 1,4-disubstituted anthraquinone analogs with amide, benzene sulfonamide, and hydrophobic functional features have been designed and synthesized. The structure of newly developed anthraquinone compounds (B141-B148) has been confirmed on FT-IR, H-1-NMR, C-13-NMR, and HR-MS spectroscopic tools. These synthesized anthraquinone compounds (B141-B148) and standard drug Mitoxantrone have been screened for biological activities using molinspiration and osiris property explorer, indicating that the compounds have smaller groups (-CH2- and -CH2-CH2-) in the side chain are orally active in comparison to other synthesized compounds. Cytotoxic study has been carried out on MCF-7, PC-3, and Hela cell lines using SRB assay. Synthesized anthraquinone compounds were found to be ineffective in the tested concentration range (10-80 tg/mL) on Hela and PC-3 cell lines. But, B147 and B148 compounds with a smaller alkyl group (-CH2-) on the side chain are screened out to be the best among all synthesized compounds in the case of MCF-7 cell line. The reactivity of developed anthraquinone compounds was further explored by computational study. HOMO-LUMO energy gap and softness of molecule with the basis set as DFT/B3LYP/6-31G(d,p) have been studied. All the synthesized compounds (B141-B148) show energy gap comparable to that of the standard drug Mitoxantrone due to some structural similarity. The binding mode and extent of binding with ct-DNA have been studied for all synthesized anthraquinone compounds (B141-B148) and Mitoxantrone at different D/P ratios using absorption, emission, and viscometric techniques. Partial intercalation mode followed by external mode of binding of drugs with ct-DNA has been observed. FT-IR spectral titrations have also been carried out for Mitoxantrone. Compounds B147 and B148 are come out as the best. The FT-IR study supports the finding of absorption, emission, and viscometric analysis, with no conformational changes observed for ct-DNA backbone. The polar functional feature attached in the side chain stabilizes the anthraquinone derivatives via external binding.