Discovery of dihydrofuranoallocolchicinoids - Highly potent antimitotic agents with low acute toxicity

Liposomal Formulation of a PLA2-Sensitive Phospholipid–Allocolchicinoid Conjugate: Stability and Activity Studies In Vitro

“…Thus, fatty acids derived from hydrolysis of liposomal phospholipids under conditions of the cytotoxicity assay (with the highest total lipid concentration used 100 µM) could promote cell proliferation. Destabilization of microtubules by free aC resulted in accumulation of cells in G2/M phase as estimated for several cell lines, which is the same manner of cell cycle arrest and apoptosis induction as colchicine [13]. We expect that liposomes carrying aC-PC prodrug release free aC, which then also follows the same mechanism of action.…”

“…Heterocyclic allocolchicinoids exhibited lower acute toxicity yet comparable cytotoxicity in vitro and anticancer activity in vivo [11][12][13][14]. Incorporation of drugs in nanosized liposomal carriers allows to decrease systemic toxicity, first of all, due to the decreased volume of distribution [15].…”

Synthesis of conjugates of (aR,7S)-colchicine with monoterpenoids and investigation of their biological activity

“…46 (d, 1 H, H (11), J = 8.0 Hz); 7.12 (d, 1 H, H (12), J = 7.9 Hz); 6.83 (s, 1 H, H(4)); 4.55 (dt, 1 H, H (7), J = 10.5 Hz, J = 7.4 Hz); 3.86 (s, 3 H, OCH 3 ); 3.85 (s, 3 H, OCH 3 ); 3.79 (s, 3 H, OCH 3 ); 3.71 (dd, 1 H, H(1´), J = 14.7 Hz, J = 8.0 Hz); 3.51 (s, 3 H, OCH 3 ); 2.58-2.52 (m, 1 H, H(5´) endo ); 2.18 (dd, 3 H, H(4´) exo , H(5), J = 9.3 Hz, J = 5.4 Hz); 2.09 (dd, 2 H, H(6), J = 13.2 Hz, J = 6.5 Hz); 2.02 (dd, 1 H, H(4´) endo , J = 13.2 Hz, J = 7.0 Hz); 1.93 (dd, 1 H, H(3´), J = 15.4 Hz, J = 8.1 Hz); 1.77-1.67 (m, 2 H, H(5a)); 1.66-1.53 (m, 4 H, H(3a), H(4a)); 1.47 (t, 1 H, H(2´) endo , J = 9.6 Hz); 1.08 (dt, 2 H, H(5´) endo , H(2´) exo , J = 14.0 Hz, J = 7.5 Hz); 0.86 (s, 3 H, С(10´)Н 3 ); 0.75 (s, 3 H, C(9´)Н 3 ); 0.73 (s, 3 H, C(8´)Н 3 ). 13 (17). The eluent for column chromatography was petroleum ether-EtOAc-EtOH (7 : 1 : 1).…”

Regioselective approach to colchiceine tropolone ring functionalization at C(9) and C(10) yielding new anticancer hybrid derivatives containing heterocyclic structural motifs

“… 12 In order to improve anticancer potency and to decrease the toxic effects of colchicine, its transformations were mainly performed at C(10), C(7), and C(4) or via destruction of the tropolone ring 13–22 . Another type of modifications of colchiceine scaffold was the formation of an extra ring, fused with the C-ring of the parent alkaloid via different approaches 23–29 . The synthetic challenges of regioselective functionalization of hydroxyl group within the tropolone of 2 and the other troponoid systems were undertaken in the past, however with different outcomes 11 , 30 .…”