Synthesis of some Mannich bases with dimethylamine and their hydrazones and evaluation of their cytotoxicity against Jurkat cells

Abstract

1-Aryl-3-dimethylamino-1-propanone hydrochlorides type mono Mannich bases, D series, and corresponding hydrazone derivatives, K series, were synthesized and their cytotoxicity was tested against Jurkat cells (transformed human T-lymphocytes). The aryl part was changed as phenyl in D1 and K1, 4-methylphenyl in D2 and K2, 4-methoxyphenyl in D3 and K3, 4-hydroxyphenyl in D4 and K4, 4-chlorophenyl in D5 and K5, 3-methoxyphenyl in D6 and K6, 4-fluorophenyl in D7 and K7, 4-bromophenyl in D8 and K8, 3-hydroxyphenyl in D9 and K9, and 2-acetylthiophene in D10 and K10. Of the compounds synthesized, K2, K3, K5, K6, K7, K8, K9, and K10 are reported for the first time. Cytotoxic activities of the D and K series were compared with each other to see alterations in bioactivity depending on the chemical structures in Jurkat cells. Cytotoxicities of the compounds synthesized were also compared with the reference compound, 5-fluorouracil (CAS 148-82-3). Mono Mannich bases, D1 (3.60 times), D2 (4.45 times), D3 (2.46 times), D4 (3.52 times), D5 (5.18 times), D6 (3.20 times), D7 (3.23 times), D8 (3.95 times), D9 (3.36 times) and D10 (3.99 times) had 2.46-5.18 times higher cytotoxic potency than the reference compound 5-fluorouracil against Jurkat cells, while hydrazones K1 (4.92 times), K2 (4.65 times), K3 (6.04 times), K4 (6.34 times), K5 (4.67 times), K6 (5.12 times), K7 (5.39 times), K8 (8.31 times), K9 (4.65 times) and K10 (8.65 times) had 4.65-8.65 times higher cytotoxic potency than the reference compound 5-fluorouracil against the same cell line. On the other hand, hydrazone compounds K1 (1.37 times), K3 (2.46 times), K4 (1.80 times), K6 (1.60 times), K7 (1.67 times), K8 (2.11 times), K9 (1.38 times), and K10 (2.17 times) had 1.37-2.46 times higher cytotoxic potency than their corresponding mono Mannich bases. The results of this study suggest that hydrazones were better compounds compared with the corresponding mono Mannich bases in terms of cytotoxicity, and they may serve as model compounds to develop new cytotoxic agents for further studies.

Coumarin derivatives: Synthesis and cation binding properties

“…1 H NMR and 13 C NMR spectra were carried on a Varian Gemini 200 (200 MHz) spectrometer using TMS as internal standard (δ = 0 ppm). IR spectra were recorded on a Perkin-Elmer 398 Spectrophotometer.…”

“…Mannich bases can display varied biological activities such as antimicrobial [1][2][3][4][5] , cytotoxic [6][7][8][9][10][11][12][13] , anticancer 14,15 , anti-inflammatory 16,17 and anticonvulsant 18,19 and DNA topoisomerase properties 20,21 . In this work, novel aminomethylcoumarin derivatives have been synthesized.…”

Synthesis and bioactivity studies of 1-aryl-3-(2-hydroxyethylthio)-1-propanones

“…These compounds have a wide range of biological activities such as carbonic anhydrase (CA, EC 4.2.1.1) inhibitory [1][2][3] , cytotoxic [2][3][4][5][6][7] , anti-inflammatory 8 and anticonvulsant activities 9,10 . The reported mechanism action of the Mannich bases are based on thiol alkylation [11][12][13][14] , interaction with enzymes that are important for antioxidant mechanisms 7 , inhibition of mitochondrial respiration 15,16 , inhibition of topoisomerase enzyme 17 as well as tubulin polimerization inhibition 18 . The CAs are that enzymes play important roles in physiological and pathological processes 19 .…”

Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities

“…Amino and hydroxy groups are available in nucleic acids, and hence a,b-unsaturated ketones may not have the genotoxic effects which are associated with various alkylating agents used in cancer chemotherapy 4 . Mannich bases are a group of compounds having various biological activities such as cytotoxic [5][6][7][8][9][10][11][12][13][14][15] anti-inflammatory 16,17 and anticonvulsant 18,19 activities. a,b-Unsaturated ketone/s available in the chemical structure of Mannich bases or produced from Mannich bases by deamination process is/are responsible for their cytotoxicities.…”