Progress and Development of C-3, C-6, and N-9 Positions Substituted Carbazole Integrated Molecular Hybrid Molecules as Potential Anticancer Agents.

Abstract

The carbazole skeleton, a key structural motif occurring naturally or chemically synthesized, showed various biological activities. Molecular hybridization based on the combination of two or more bioactive pharmacophores has been an important tool to convert the potent structural leads to form new hybrid compounds with improved biological activity. In recent years, modifications/ substitutions of the carbazole motif at C-3, C-6, and N-9 positions have been carried to develop novel carbazole-based potential anticancer agents in the therapy of cancer. In the last fifteen years, several compounds based on carbazole core integrated into pharmacologically active molecular hybrid having active pharmacophore such as1,3,4-thiadiazole, thiazole, guanidine, sulfonamides, glyoxamides, imidazoles, phenanthrenes, rhodamines, chalcones, imidazopyridine, platinum, 2-H-chromen- 2-one, hydrazones, piperazines, isoxazole-thiadiazole, pyrazoles, etc. have been synthesized showing anticancer profile at sub-micromolar to nano-molar concentrations. We have thoroughly reviewed the design, progress, and development of C-3, C-6, and N-9 positions substituted carbazole derivatives integrated with various medicinally active pharmacophore as potential anticancer agents evaluated against various cancer cell lines. Additionally, the anticancer mechanism and in vivo activity of the reported compounds have been discussed. This study will support in designing of new pharmacophore that can be linked to the carbazole motif for the development of new, potent, and target-specific anticancer drugs with improved pharmacokinetics and minimal side effects.