Compounds Combining Aminoadamantane and Monoterpene Moieties: Cytotoxicity and Mutagenic Effects

Abstract

A series of secondary amines combining monoterpenoid and aminoadamantane moieties have been synthesized. Their cytotoxic activity against human cancer cells CEM-13, MT-4, and U-937 has been studied for the first time. Most of the obtained compounds exhibited a significant cytotoxic activity with the median cytotoxic dose (CTD50) ranging from 6 to 84 µM. The most promising results were obtained for compound 2b which was synthesized from 1-aminoadamantane and (-)-myrtenal and revealed a high activity against all tumor lines used (CTD50 = 12 ÷ 21 µM) along with low toxicity with respect to MDCK cells (CTD50 = 1500 µM). The synthesized amines do not exert the genotoxic effect on cells of the biosensor strain based on recombinant E. coli cells bearing the pRAC-gfp plasmid.

New inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 7-hydroxycoumarin and monoterpenoid moieties

“…[16][17][18] Furthermore, many researchers are interested in developing new cytotoxic agents from this class of compounds. [19][20][21][22] The molecules of the library were screened to the binding pocket of the crystal structure of Tdp1 (PDB ID: 1MU7, resolution 2.0 Å). 23 From the InterBioScreen natural product library 10179 compounds were used.…”

“…13 C-NMR (CDCl 3 , δ C ): 155.60 (s, C(1)); 160.48 (s, C(2)); 124.28 (s, C(3)); 156.23 (s, C(4)); 112.21 (s, C(5)); 125.28 (d, C(6)); 112.85 (d, C(7)); 161.29 (s, C(8)); 101.67 (d, C(9)); 30.24 (t, C(10)); 22.47 (t, C(11)); 31.93 (t, C(12)); 71.00 (t, C(13)); 143.07 (s, C (14) 6)). 13 C-NMR (CDCl 3 , δ C ): 155.10 (s, C(1)); 161.28 (s, C(2)); 111.74 (d, C(3)); 152.44 (s, C(4)); 113.37 (s, C(5)); 125.21 (d, C(6)); 112.91 (d, C(7)); 161.96 (s, C(8)); 101.75 (d, C(9)); 18.51 (q, C(10)); 71.06 (t, C(11)); 142.96 (s, C(12)); 121.30 (d, C(13)); 31.18 (t, C(14)); 40.70 (d, C(15)); 37.99 (s, C(16)); 43.10 (d, C(17)); 31.39 (t, C(18)); 26.01 (q, C(19)); 20.96 (q, C (20) (18), 3H-C(20)); 5.03 (s, 2H, H-C(11)); 6.12 (q, 1H, J(3,10)=1.2, H-C(3)); 6.63 (s, 2H, H-C(13), H-C(17)); 6.87 (d, 1H, J(9,7)=2.5, H-C(9)); 6.92 (dd, 1H, J(7,6)=8.8, J (7,9)=2.5, H-C(7)); 7.49 (d, 1H, J(6,7)=8.8, H-C(6)). 13 C-NMR (CDCl 3 , δ C ): 155.11 (s, C(1)); 161.06 (s, C(2)); 112.04 (d, C(3)); 152.33 (s, C(4)); 113.76 (s, C(5)); 125.47 (d, C(6)); 112.78 (d, C (7)); 161.50 (s, C(8)); 101.80 (d, C(9)); 18.52 (q, C(10)); 70.64 (t, C(11)); 131.22 (s, C(12)); 104.57 (d, C(13), C(17)); 153.46 (s, C (14), C(16)); 137.96 (s, C(15)); 56.07 (q, C(18), C(20)); 60.72 (q, C (19) …”

“…All of the target compounds reported in this paper have a purity of no less than 95%.Synthesis of (1S,5R)-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbaldehyde (+)-18. (+)-Myrtenal (+)-18 was synthesized according to the procedure 33 by oxidation of (+)-α-pinene(20…”

“…(d, C(16), C(20)); 128.57 (d, C(17), C(19)); 128.13 (d, C(18)). HRMS: 306.1249 ([M] + , m/z calcd for C 20 H 18 O 3 306.1251).3-(((1R,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)methoxy)-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one ((-)-24c).…”

A review on genotoxic and mutagenic effects of monoterpenes

“…In a study, a series of secondary amines combining monoterpenoid and amino adamantane moieties have been synthesized and tested for cytotoxic effects against human cancer cells CEM-13, MT-4, and U-937, which revealed significant cytotoxic rather than a genotoxic effect on cells (Suslov et al 2015). In normal human skin explants obtained from young healthy women (n = 7) Thymus vulgaris leaf extract and thymol were found to prevent UV-induced skin damage.…”