Synthesis and Antiproliferative Screening Of Novel Analogs of Regioselectively Demethylated Colchicine and Thiocolchicine.

Colchicine, a pseudoalkaloid isolated from , has been identified as a potent anticancer agent because of its strong antimitotic activity. It was shown that colchicine modifications by regioselective demethylation affected its biological properties. For demethylated colchicine analogs, 10-demethylcolchicine (colchiceine, ) and 1-demethylthiocolchicine (), a series of 12 colchicine derivatives including 5 novel esters (- and -) and 4 carbonates (- and -) were synthesized. The antiproliferative activity assay, together with evaluation of physicochemical properties, confirmed attractive biological profiles for all obtained compounds. The substitutions of H-donor and H-acceptor sites at C1 in thiocolchicine position provide an efficient control of the hydration affinity and solubility, as demonstrated for anhydrate , hemihydrate and monohydrate .