A REVIEW ON SYNTHETIC PATHWAYS AND PHARMACOLOGICAL PROPERTIES OF CINNOLINE DERIVATIVES

Cinnoline is an emerging benzo-fused diazine scaffold with great versatility in heterocyclic and medicinal chemistry owing to its aromatic ring deficiency of electrons, hydrogen-bonding capability, and bio-isosteric relationship with quinoline and pyridine. In the last decade, significant progress has been made in the synthesis, functionalization, and pharmacological study of cinnoline derivatives. The goal of this review is to highlight some of the classical and modern synthetic strategies, including diazotization-cyclization, Fischer-Hepp rearrangement, metal-catalyzes annulation, cycle condensation of hydrazines, and multicomponent and green methodologies, such as microwave, ultrasound, ionic liquids, and photocatalysis. These approaches increase the structural diversity with significant improvements in atom economy and sustainability. Parallel biological investigations have highlighted to wide pharmacological potential of cinnoline derivatives. In addition to antimicrobial and antitubercular properties, various anticancer, anti-inflammatory, analgesic, and neuroactive activities have been reported. The main contribution to potency and selectivity came from substitution patterns at the 3- and 4-positions, with beneficial roles being played by N-oxide formation and hydrophobic, or sulfonamide functions. Moreover, an emerging hybrid architecture involving cinnoline and other privileged heterocycles has opened new avenues for multitarget drug discovery. Moving forward, cinnoline chemistry is also developing in the fields of green chemistry, advanced imaging probes, and nanoscale-mediated delivery systems. Based on its synthetic applicability and broad biological relevance, cinnoline can be considered a crucial platform for the development of novel biological therapeutics.