Synthesis, Structural Characterization and Biological Evaluation of 3-Amino-5-(5-oxo-5H-benzo[a]phenoxazin-6-ylamino)benzoic acid Derivatives

Abstract

1,4-Naphthoquinones are exceptional building blocks in organic synthesis and have been used to synthesize several well-known pharmaceutically active agents. Compounds containing oxygen, nitrogen or sulfur atoms inside the rings are attracting much attention and interest due to their biological importance. A series of 3-amino-5-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylamino)benzoic acid derivatives were synthesized by the Michael addition of 2,3-dichloronaphthalene-1,4-dione and 3,5-diaminobenzoic acid. All the synthesized compounds are screened for their bioactivity through molecular docking, cytotoxicity (against HeLa) and antioxidant activity. DPPH and ABTS evaluation procedures are employed to assess the antioxidant activity. Among the synthesized 3-amino-5-(3-chloro-1, 4-dioxo-1, 4-dihydronaphthalen-2-ylamino)benzoic acid derivatives (1, 2, 3a-g), compound 3d exhibited the highest inhibition of 75 % and 83 % in the DPPH and ABTS antioxidant activity evaluation, respectively. Compound 3d exhibited better glide energy and E model scores when docked with HDAC8 using GLIDE program. Cytotoxicity of the synthesized compounds was studied against cervical cancer cell line (HeLa) and compound 3d showed the maximum inhibition and displayed a better activity than the standard drug.