Benzo[α]phenoxazines and benzo[α]phenothiazine from vitamin K3: synthesis, molecular structures, DFT studies and cytotoxic activity

Synthesis and characterization of fluorescent benzo[alpha]phenoxazines viz., M-1B (10-chloro-6-methyl-7a, 11a-dihydro-5H-benzo[alpha]phenoxazin-5-one), M-2B 6,10-dimethyl-7a,11a-dihydro-5H-benzo[alpha]phenoxazin- 5-one), M-3B (6-methyl-7a,11a-dihydro-5H-benzo[alpha]phenoxazin-5-one) and benzo[alpha]phenthiazine, M-4B (6-methyl-5H-benzo[alpha]phenothiazin-5-one) were carried out. H-1 and C-13 chemical shifts were assigned from the 2DgHSQCAD NMR experiments. Compound M-1B crystallizes in the orthorhombic space group P2(1)2(1)2(1), while M-2B and M-4B crystallize in the monoclinic space group P2(1)/c. The crystal network of M-1B showed slipped pi-pi stacking and Cl center dot center dot center dot Cl interactions, while M-2B facilitated ladder like pi-pi stacked polymeric chains. The C center dot center dot center dot S contacts were observed in the crystal environment of M-4B. All these structures possess C-H center dot center dot center dot O interactions. Electronic structure and charge distribution in terms of molecular electrostatic potential and frontier orbital analyses based on the MO6-2X based density functional theory further showed that monomer and dimer structures are in keeping with the single crystal X-ray data and provide insights for the growth of the crystal network. Antiproliferative activity of M-1B-M-4B was determined from the MTT assay against a human breast adenocarcinoma cell line (MCF-7), human carcinoma cell line (HeLa) and normal skin cell line. All these compounds showed significant cytotoxic activity against MCF-7 and HeLa by inducing apoptosis and thus can be viewed as potential candidates for antitumor therapy. Compounds M-2B and M-4B were further found to be topoisomerase II inhibitors.