Synthesis, Characterization, Crystal Structure and Anti‐TB and Anticancer Applications of Redox Active Phenanthroline Derivatized With Methyl‐, Ethyl‐, and Benzyl Carbazates

Developing new molecules for treating bacterial infections and cancer disease is an important area of exploration as both types of cells often develop resistance to known drug candidates. Synthesis, structural characterization, and bioactivity of heterocyclic compounds 6-[2-(benzyloxycarbonyl)diazen-1-yl]-1-10-phenanthroline-5-one (BCDPO) along with 6-[2-(ethoxycarbonyl)diazen-1-yl]-1-10-phenanthroline-5-one (ECDPO) and 6-[2-(methoxycarbonyl)diazen-1-yl]-1-10-phenanthroline-5-one (MCDPO), which are 1,10-phenanthroline-5,6-dione (PD) derivatized with benzyl carbazate (BC), ethyl carbazate (EC), and methyl carbazate (MC), respectively, are studied. The BCDPO crystallized in triclinic system P-1 space group, the supramolecular BCDPO arrays stabilized involving noncovalent O···H and N···H hydrogen bond interactions as well as π-π stacking aromatic interactions. Redox properties studied through cyclic voltammetry and spectroelectrochemistry. The benzyl analog showed better anti-tuberculosis (TB) activity than the methyl and ethyl analogs. The BCDPO shows good minimum inhibitory concentration (MIC) against Mycobacterium tuberculosis (Mtb), which is equivalent to clinically used rifampicin but better than the one of the clinically used drug candidates ethambutol. These compounds exhibit promising anticancer activity against the murine-triple-negative breast cancer (4T1), human breast cancer (MCF-7), and human prostate cancer (PC-3) cancer cell lines. Fluorescence confocal imaging and flow cytometry studies are performed to monitor the compound-induced reactive oxygen species (ROS) generation, nuclear fragmentation, and apoptosis in cancer cell death. The carbazate functionalized phenanthroline derivatives developed are showing promising anti-TB and anticancer activities.