Synthesis and antiproliferative screening of novel doubly modified colchicines containing urea, thiourea and guanidine moieties

Novel Double-Modified Colchicine Derivatives Bearing 1,2,3-Triazole: Design, Synthesis, and Biological Activity Evaluation

“…Resistance indexes (RI) were calculated (ratio of IC 50 value for LoVo/DX cell line to IC 50 value for LoVo cell line) for evaluation of the ability of the tested compounds to break the drug resistance of the LoVo/DX line. 56 The RI values obtained for the studied derivatives are shown in Table 1 As we reported earlier 13,14,38,39 and as confirmed by the results presented here, replacement of an −OMe group with an −NHMe group at position C10 increases the cytotoxicity of native colchicine 1. In addition, the majority of the 10-Nmethylaminocolchicines containing the triazole ring showed antiproliferative activity in the nanomolar values against three out of four tumor cell lines tested (Table 1).…”

“…The resistance coefficients (RI) determined for the 7modified 10-N-methylaminocolchicine derivatives obtained by us 13,14,38,39 indicate an interesting relationship. The majority of the compounds containing amide, urethane, urea bond, etc.…”

“…In view of the above, 1,2,3-triazoles represent a promising scaffold in the search for compounds with biological properties improved over those of the starting substances in which they could replace and mimic a certain moiety. Therefore, continuing our research on modifications of 10-N-methylaminocolchicine at position C7, 13,14,38,39 and together with the reports on the cytotoxicity of colchicines with a triazole ring on C7 carbon (both those with simple substituents and more complex conjugates with ferrocenyl and ruthenocenyl), 40−43 we synthesized 7-azido-10-N-methylaminocolchicine 4 and obtained a series of 39 derivatives (5−43) containing 1,2,3-triazole core. It should be noted that the double-modified derivatives of colchicine with a triazole ring have not been previously described.…”

“…Among the presented derivatives, the most interesting seem to be compounds 30 and 34 with high SI values and low IC 50 values. Important compounds, in terms of biological properties, are also compound 8 (aminomethyltriazole) and its amides (29,31,33,35,36) and carbamates (37)(38)(39)(40)(41)43) along with esters of hydroxymethyltriazole (24−27). The results clearly indicate that the appropriate selection of the side chain on C4′ carbon of 7-triazole-10-N-methylaminocolchicine allows obtaining derivatives with increased therapeutic potential compared to that of unmodified colchicine 1 or doxorubicin and cisplatin.…”

New Potential Agents for Malignant Melanoma Treatment—Most Recent Studies 2020–2022

“…As a result, modifications to the structure of ibrutinib are of great interest to scientists looking for anticancer drugs [ 68 ]. Based on the literature data, the thiourea moiety was introduced, which ensures selectivity, effectiveness, and favorable physicochemical parameters [ 69 , 70 , 71 , 72 , 73 ]. Compound (32) exhibited the highest activity against melanoma cell line B16 with an IC 50 = 6.07 ± 1.06 µM [ 74 ].…”