Novel fluorocurcuminoid-BF2 complexes and their unlocked counterparts as potential bladder anticancer agents-synthesis, physicochemical characterization, and in vitro anticancer activity

Low efficiency of anticancer drugs and their toxicity in normal tissues has motivated further study on safe and effective modern anticancer agents. In the presented study, the design and synthesis of a library of 14 fluorinated curcumin (F-CUR) derivatives and their F-CUR-BF2 adducts are presented. Chemical modifi-cations of curcumin derivatives included the introduction of BF2 unit to the diketone group, as well as the substitutions of one or two fluorine atoms in different positions of the phenyl rings. The obtained com-pounds were broadly characterized using ESI HRM spectrometry, 1D and 2D NMR techniques ( 1 H, 13 C, 19 F, HMBC, HSQC and COSY), Fourier transform infrared spectroscopy (FTIR), and melting points. More-over, the purity of curcumin derivatives was determined using TLC and HPLC. Novel curcumin derivatives were subjected to biological studies against two bladder cancer cell lines 5637 and SCaBER using the MTT assay and then the structure-activity relationship was established.Our study demonstrated that it is the presence of the BF2 moiety in the curcumin derivative structure, which determines the cytotoxic effect on cancer cells as the compounds with unchanged 3,5-diketone unit did not appear active in cancer cells. In addition, higher activities among the studied compounds were observed for curcumin-BF2 adducts with methoxy than with the hydroxy or fluorine group; or for compounds containing one fluorine rather than two fluorine groups. Moreover, it has become evident that the position of substituents relative to each other plays a significant role. To sum up, all BF2 adducts ap-peared more effective than curcumin, with the most cytotoxic compound belonging to F-CUR-BF2 adducts with 3-fluoro-4-methoxyphenyl groups in its structure and IC50 values of 6.4 9 +/- 0.4 9 mu M and 3.31 +/- 0.51 mu M after 24h incubation for 5637 and SCaBER cancer cell lines, respectively. The four most active F-CUR-BF2 derivatives and their F-CUR analogs were subjected to stability tests. Based on the stress tests, the susceptibility of these compounds to various environmental factors, such as hydrolytic and oxidizing agents, light, and temperature, were assessed. (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )