Quinoline and ferrocene conjugates: Synthesis, computational study and biological evaluations

Novel O‐alkylated quinoline and N‐alkylated 4‐quinolone derivatives attached to the ferrocene moiety through 4,1‐ (7a–d, 8a–d and 12a–d) and 1,4‐disubstituted (9a, 9b, 10a and 10b) 1,2,3‐triazole moiety were synthesized. The observed regioselectivity of O‐ vs. N‐alkylation was explored by the use of NMR and computational techniques. Among the N‐alkylated derivatives, the quinolone‐ferrocene conjugate 9a displayed marked activities against chronic myeloid leukemia in blast crisis (K562) and Burkitt lymphoma (Raji). The 6‐chloroquinolone‐ferrocene conjugate 12c, with selective inhibitory activity on Raji cells and no cytostatic effect on normal MDCK1 cells was highlighted as the most promising anticancer organometallic complex in a group of O‐alkylated quinolines. O‐ and N‐regioisomers of new quinoline‐ferrocene conjugates exhibit different cytostatic activity.