Synthesis of 1-(Indol-2-yl)-phenoxazine hybrids from quinacetophenone precursors and their biological evaluation as DNA intercalating agents

• Published in: Journal of molecular structure 2020-10, Vol.1217, p.128311, Article 128311
• Main Authors: Nunewar, Saiprasad N., Kotla, Naveen, Lakshmi Uppu, Jaya, Dixit, Apoorva, Pooladanda, Venkatesh, Godugu, Chandraiah, Tangellamudi, Neelima D.
• Format: Article
• Language: English
• Subjects: Aza-Michael attack; DNA intercalation; Phenoxazine hybrids; Quinacetophenone
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.128311

An operationally simple reaction between quinacetophenone and aniline derivatives in the presence of triethylamine at room temperature afforded 1-(indol-2-yl)-phenoxazine hybrids in good yields. This unique transformation proceeds via sequential aza-Michael attack and imine formation to yield 1-(indol-2-yl)-phenoxazine hybrids. The most plausible reaction mechanism was established based on the mechanistic studies carried out with Mass spectrometry. The synthesized molecules were subjected to in-vitro anti-proliferative evaluation on various cancer cell lines by MTT assay where compound 8 was found to display signifiacnt IC50 value of 3.71 ± 0.57 μM on A-549 cell line. The ability of compound 8 to intercalate DNA was also confirmed by DNA Nanodrop method and viscosity experimental studies. [Display omitted] •An operationally simple reaction between quinacetophenone and aniline derivatives to afforded 1-(indol-2-yl)-phenoxazine hybrids in good yields is presented.•The most plausible reaction mechanism was established based on the mechanistic studies carried out with Mass spectrometry.•MTT assay reveals compound 8 to display significant IC50 value of 3.71 ± 0.57 μM on A-549 cell line.•The ability of 8 to intercalate DNA was also confirmed by DNA Nanodrop method and viscosity experiments.