Mannich bases of hydroxycoumarins: synthesis, DFT/QTAIM computational study and assessment of biological activity

Abstract

Mannich bases derived from hydroxycoumarins as interesting scaffolds for several applications.

Anticancer Activity of Mannich Bases: A Review of Recent Literature

“…series of other analogous 8‐hydroxyquinoline Mannich bases 88 and 89 (X=H or Cl; Z=O or CH 2 ) [112] . Aminomethylated 7‐hydroxycoumarins 90 (Figure 11) were poor antiproliferative agents against HeLa cells, while two aminomethylated 6,7‐dihydroxycoumarin (esculetin) derivatives 91 (R 1 =CH 3 ) (Figure 11) inhibited the growth of the same cancer cells in the range of 45 to 60 % at 100 μM [113] . Analogous compounds 91 (R 1 =H, CH 3 or CF 3 ) were shown to generally exhibit better antiproliferative activity than the parent esculetin against A549 non‐small cell lung carcinoma and B16 mouse melanoma cell lines [114] .…”

“…[112] Aminomethylated 7-hydroxycoumarins 90 (Figure 11) were poor antiproliferative agents against HeLa cells, while two aminomethylated 6,7-dihydroxycoumarin (esculetin) derivatives 91 (R 1 = CH 3 ) (Figure 11) inhibited the growth of the same cancer cells in the range of 45 to 60 % at 100 μM. [113] Analogous compounds 91 (R 1 = H, CH 3 or CF 3 ) were shown to generally exhibit better antiproliferative activity than the parent esculetin against A549 non-small cell lung carcinoma and B16 mouse melanoma cell lines. [114] Further examples of phenolic Mannich bases of heterocyclic substrates with anticancer activity include aminomethylated 4-hydroxy-1,8-naphthyridines 92 (R 1 = CH 3 or C 6 H 5 ), [115] aminomethylated 5,7-dihydroxyquinolin-4-ones 93, [116] or aminomethylated 6-hydroxyaurones 94 (compound with NR 2 = N(CH 3 )CH 2 C 6 H 5 and Ar = 3,4,5-(H 3 CO) 3 C 6 H 2 had IC 50 = 3.9 μM against PC-3 cells) [117] (Figure 11).…”