European journal of medicinal chemistry · 2019
Recent developments on (-)-colchicine derivatives: Synthesis and structure-activity relationship.
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Ghawanmeh Abdullah A, Al-Bajalan Hussein M, Mackeen Mukram Mohamed, Alali Feras Q, Chong Kwok Feng
Аннотация
(-)-Colchicine, an anti-microtubulin polymerization agent, is a valuable medication and the drug of choice for gout, Behçet's disease and familial Mediterranean fever. It has a narrow therapeutic index due to its high toxicity towards normal cells. Nonetheless, numerous (-)-colchicine derivatives have been synthesized and studied for their structure-activity relationship and preferential toxicity. Different functional groups such as amides, thioamides, N-arylurea and 8,12-diene cyclic have been incorporated into (-)-colchicine, resulting in derivatives (with moieties) that include electron-withdrawing and electron-donating groups. This review article focuses on recent developments in the chemical synthesis of (-)-colchicine derivatives, the substituents used, the functional groups linked to the substituents, the moieties and biological studies. Moreover, the current classification of derivatives based on the (-)-colchicine rings, namely ring A, B, and C (-)-colchicine derivatives, is discussed. This work demonstrates and summarizes the significance of (-)-colchicine derivatives in the biological field, and discusses their promising therapeutics for the future.