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1-(2,4-Dihydroxyphenyl)-1-ethanone Hydrazone Derivatives as Notable Butyrylcholinesterase Inhibitors.

Byline: Muhammad Athar Abbasi, Sikander Khan Niazi, Aziz-Ur-Rehman, Sabahat Zahra Siddiqui, Ghulam Hussain, Shahid Rasool, Muhammad Ashraf, Jamil Rahman and Khalid Mohammed Khan

Abstract: Azomethine group of Schiff bases is known to express valuable biological activities. 1- (2,4-Dihydroxyphenyl)-1-ethanone N'-substituted hydrazone derivatives, 4a-s, were synthesized in multistep. The starting material 2,4-dihydroxyacetophenone (1) was stirred with hydrated hydrazine to yield 1-(2,4-dihydroxyphenyl)-1-ethanone hydrazone (2) which was further reacted with (un)substituted benzaldehydes, 3a-s, to acquire the target molecules, 4a-s. Moreover, the synthesized derivatives 4a-s was characterized via IR, EI-MS, 1H-NMR and 13C-NMR spectral techniques. Most of the compounds were found to be valuable inhibitors of butyrylcholinesterase enzyme.

Keywords: 2,4-Dihydroxyacetophenone, Butyrylcholinesterase, Schiff bases, 1H-NMR and 13C-NMR.

Introduction

The molecules bearing azomethine group, commonly known as Schiff bases are found to be active against various microbes and are pharmacologically important in this respect. The list of various activities possessed by such type of molecules include anti-bacterial, anti-inflammatory etc. Medicinal and agricultural field have also been entertained by these molecules [1-10].

Butyrylcholinesterase (BChE, EC 3.1.1.8), a group of enzymes including serine hydrolases, takes part in hydrolysis of acetylcholine, the neurotransmitter and hence termination of nerve impulse. BChE has also been found to exist in Alzheimer's plaques in substantial amount as compared to normal age related non dementia of brains. The BChE inhibitors enhance the concentration of acetylcholine reversibly or irreversibly and thought to be important drug candidates for Alzheimer's diseases [11-12].

The structural effects on biological activities [13-17], have prompted us to synthesize molecules bearing two azomethine groups and to evaluate them as anti-enzymatic agents. The low inhibitory concentration (IC50) values of anti-enzymatic activity favored good butyrylcholinesterase enzyme inhibition activity of the synthesized derivatives.

Experimental

General

TLC plates prepared by silica gel 60 F254 were used to develop TLC using different ratios of AcOEt/n-hexane for purity confirmation after visualization under UV254. The spectra were recorded as IR by pellet method on Jasco-320-A spectrophotometer, NMR on Bruker spectrometer (1H-NMR at 400 MHz and 13C-NMR at 100 MHz in CD3OD) and EIMS on JMS-HX-110 spectrometer. Compounds were supported by uncorrected melting points noted on Griffin-George apparatus. All the reagents were procured from Alfa Aesar and Sigma- Aldrich and solvents were of analytical grade.

Procedure for synthesis of 1-(2,4-Dihydroxyphenyl)-1-ethanone hydrazone (2)

2,4-Dihydroxyacetophenone (1; 0.0019 mol) was taken in a 100 mL round bottom flask containing 22 mL MeOH. Equimolar quantities of 80% hydrated hydrazine and a few drops of glacial AcOH were added and product was formed in 3-4 hours and confirmed by the developed TLC. Volume of mixture was reduced to 7-10 mL by distillation and then excess of distilled water was added to afford light yellow precipitates of 1-(2,4-dihydroxyphenyl)-1-ethanone hydrazone 2 as amorphous solid which was filtered and washed with distilled water and dried.

General procedure for synthesis of 1-(2,4-Dihydroxyphenyl)-1-ethanone N'-substituted hydrazone (4a-s)

1-(2,4-Dihydroxyphenyl)-1-ethanone hydrazone (2; 0.0001 mol) was mixed with 13 mL MeOH in a 50 mL round bottom flask.

A few drops of glacial AcOH and (un)substituted benzaldehydes (3a-s, 0.0001 mol) were added and stirrd for 3-4 hours. Completion of reaction was confirmed through developed TLC and then excess of cold distilled water was added to quench the precipitates. The precipitates of the titled compounds were filtered, washed by distilled water and dried.

Spectral Analysis:

1-(2,4-Dihydroxyphenyl)-1-ethanone hydrazone (2)

Light yellow amorphous solid; Yield: 76 %; M.P.: 162-164 C; Mol. formula: C8H10N2O2; Mol. mass: 166 gmol-1; IR (KBr, max/cm-1): 3329 (N-H), 3246 (O-H), 3112 (Ar C-H), 1661 (C=N), 1613 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 7.26 (d, J = 8.8 Hz, 1H, H-6), 6.28 (dd, J = 8.4, 2.4 Hz, 1H, H-5), 6.23 (d, J = 2.4 Hz, 1H, H-3), 2.16 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 164.8 (C-4), 162.9 (C-2), 161.1 (C-7), 132.1 (C-6), 109.3 (C-5), 108.2 (C-1), 104.5 (C-3), 14.7 (C-8); EIMS (m/z): 166 [M]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'- benzylidenehydrazone (4a)

Bright yellow amorphous solid; Yield: 78 %; M.P.: 154-156 C; Mol. formula: C15H14N2O2; Mol. mass: 254 gmol-1; IR (KBr, max/cm-1): 3249 (O-H), 3045 (Ar C-H), 1664 (C=N), 1617 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.03 (s, 1H, H- 7'), 7.94 (dd, J = 7.6, 1.6 Hz, 2H, H-2' and H-6'), 7.74- 7.69 (m, 3H, H-3' to H-5'), 7.25 (d, J = 8.4 Hz, 1H, H-6), 6.27 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.23 (d, J = 2.0 Hz, 1H, H-3), 2.14 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 171.3 (C-7), 165.8 (C-2), 163.6 (C-4), 153.4 (C-7'), 139.2 (C-1'), 132.4 (C-6), 130.5 (C-3' and C-5'), 128.7 (C-4'), 124.6 (C-2' and C-6'), 109.9 (C-5), 108.4 (C-1), 106.1 (C-3), 15.3 (C-8); EIMS (m/z): 254 [M]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 104 [C7H6N]+, 83 [C4H3O2]+, 80 [C5H4O]+, 77 [C6H5]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2-methylbenzylidene)hydrazone (4b)

Dark yellow amorphous solid; Yield: 81 %; M.P.: 160-162 C; Mol. formula: C16H16N2O2; Mol. mass: 268 gmol-1; IR (KBr, max/cm-1): 3259 (O-H), 3033 (Ar C-H), 1659 (C=N), 1605 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.32 (s, 1H, H- 7'), 7.73 (ddd, J = 8.8, 2.0 Hz, 1H, H-5'), 7.64 (d, J = 8.0 Hz, 1H, H-6'), 7.31 (ddd, J = 7.6, 1.6 Hz, 1H, H- 4'), 7.26 (d, J = 8.0 Hz, 1H, H-6), 7.21 (d, J = 7.6 Hz, 1H, H-3'), 6.25 (dd, J = 8.0, 2.0 Hz, 1H, H-5), 6.24 (d, J = 2.4 Hz, 1H, H-3), 2.41 (s, 3H, CH3-8'), 2.15 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 171.6 (C-7), 165.3 (C-2), 163.2 (C-4), 153.7 (C-7'), 139.7 (C-2'), 134.6 (C-1'), 132.3 (C-6), 129.5 (C-4'), 128.7 (C-6'), 126.4 (C-3'), 125.3 (C-5'), 109.7 (C-5), 108.2 (C-1), 106.4 (C-3), 20.6 (C-8'), 15.5 (C-8); EIMS (m/z): 268 [M]+, 118 [C8H8N]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 91 [C7H7]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(3-methylbenzylidene)hydrazone (4c)

Bright yellow amorphous solid; Yield: 82 %; M.P.: 158-160 C; Mol. formula: C16H16N2O2; .Mol.mass: 268 gmol; IR (KBr, max/cm): 3267 (O-H), 3028 (Ar C-H), 1668 (C=N), 1602 (Ar C=C); H- NMR (400 MHz, CD3OD, d in ppm): 8.02 (s, 1H, H- 7'), 7.56 (d, J = 8.0 Hz, 1H, H-6'), 7.27 (d, J = 8.8 Hz, 1H, H-6), 7.23 (t, J = 8.8 Hz, 1H, H-5'), 7.15 (d, J = 8.0 Hz, 1H, H-4'), 6.76 (s, 1H, H-2'), 6.29 (dd, J = 8.8, 2.0 Hz, 1H, H-5), 6.25 (d, J = 2.0 Hz, 1H, H- 3), 2.35 (s, 3H, CH3-8'), 2.16 (s, 3H, CH3-8); 13C- NMR (100 MHz, CD3OD, d in ppm): 172.4 (C-7), 164.3 (C-2), 163.1 (C-4), 153.6 (C-7'), 141.3 (C-3'), 139.7 (C-1'), 132.6 (C-6), 129.7 (C-4'), 129.1 (C-2'), 128.5 (C-5'), 126.2 (C-6'), 109.6 (C-5), 108.3 (C-1), 106.2 (C-3), 19.5 (C-8'), 15.4 (C-8); EIMS (m/z): 268 [M]+, 118 [C8H8N]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 91 [C7H7]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(4-methylbenzylidene)hydrazone (4d)

Yellow amorphous solid; Yield: 79 %; M.P.: 166-168 C; Mol. formula: C16H16N2O2; Mol. mass: 268 gmol-1; IR (KBr, max/cm-1): 3265 (O-H), 3025 (Ar C-H), 1664 (C=N), 1601 (Ar C=C); H-NMR (400 MHz, CD3OD, d in ppm): 8.01 (s, 1H, H-7'), 7.65 (d, J = 8.4 Hz, 2H, H-2' and H-6'), 7.21 (d, J = 8.8 Hz, 2H, H-3' and H-5'), 7.27 (d, J = 8.4 Hz, 1H, H- 6), 6.27 (dd, J = 8.0, 2.0 Hz, 1H, H-5), 6.22 (d, J = 2.8 Hz, 1H, H-3), 2.33 (s, 3H, CH3-8'), 2.15 (s, 3H, CH3-8); C-NMR (100 MHz, CD3OD, d in ppm): 171.5 (C-7), 165.6 (C-2), 163.5 (C-4), 153.5 (C-7'), 139.4 (C-4'), 132.7 (C-6), 129.4 (C-1'), 130.4 (C-3' and C-5'), 125.2 (C-2' and C-6'), 109.6 (C-5), 108.3 (C-1), 106.2 (C-3), 19.6 (C-8'), 15.3 (C-8); EIMS (m/z): 268 [M]+, 118 [C8H8N]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2], 80 [C5H4O], 91 [C7H7], 67 [C4H3O], 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2- hydroxybenzylidene)hydrazone (4e)

Greenish yellow amorphous solid; Yield: 84 %; M.P.: 224-226 C; Mol. formula: C15H14N2O3; Mol. mass: 270 gmol-1; IR (KBr, max/cm-1): 3260 (O- H), 3021 (Ar C-H), 1662 (C=N), 1607 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.35 (s, 1H, H- 7'), 7.91 (d, J = 7.6 Hz, 1H, H-6'), 7.56 (dd, J = 7.6, 1.6 Hz, 1H, H-3'), 7.27 (d, J = 8.0 Hz, 1H, H-6), 7.23 (dt, J = 7.6, 2.0 Hz, 1H, H-4'), 6.90 (dt, J = 7.6, 2.0 Hz, 1H, H-5'), 6.26 (dd, J = 8.0, 2.0 Hz, 1H, H-5), 6.21 (d, J = 2.0 Hz, 1H, H-3), 2.17 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 174.2 (C- 7), 165.5 (C-2), 163.7 (C-4), 158.3 (C-7'), 148.9 (C- 2'), 132.6 (C-6), 127.3 (C-4'), 126.1 (C-6'), 121.1 (C- 5'), 120.4 (C-1'), 122.3 (C-3'), 109.6 (C-5), 108.3 (C- 1), 106.2 (C-3), 15.3 (C-8); EIMS (m/z): 270 [M]+, 120 [C7H6NO]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 93 [C6H5O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(3-hydroxybenzylidene)hydrazone (4f)

Yellow amorphous solid; Yield: 81 %; M.P.: 228-230 C; Mol. formula: C15H14N2O3; Mol. mass: 270 gmol-1; IR (KBr, max/cm-1): 3268 (O-H), 3024 (Ar C-H), 1660 (C=N), 1609 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 8.44 (s, 1H, HO-3'), 8.13 (s, 1H, H-7'), 7.71 (dd, J = 7.6, 1.6 Hz, 1H, H- 6'), 7.28 (d, J = 8.8 Hz, 1H, H-6), 7.22 (t, J = 7.6 Hz, 1H, H-5'), 6.81 (dd, J = 8.4, 1.6 Hz, 1H, H-4'), 6.75 (s, 1H, H-2'), 6.25 (dd, J = 8.8, 2.0 Hz, 1H, H-5), 6.21 (d, J = 2.0 Hz, 1H, H-3), 2.14 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 172.6 (C- 7), 164.4 (C-2), 163.2 (C-4), 159.4 (C-3'), 153.1 (C- 7'), 132.8 (C-6), 129.3 (C-1'), 128.5 (C-5'), 124.2 (C- 2'), 122.1 (C-6'), 120.3 (C-4'), 109.7 (C-5), 108.1 (C- 1), 106.4 (C-3), 15.3 (C-8); EIMS (m/z): 270 [M]+, 120 [C7H6NO]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 93 [C6H5O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(4-hydroxybenzylidene)hydrazone (4g)

Yellow amorphous solid; Yield: 79%; M.P.: 248-250 C; Mol. formula: C15H14N2O3; Mol. mass: 270 gmol-1; IR (KBr, max/cm-1): 3264 (O-H), 3025 (Ar C-H), 1663 (C=N), 1609 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 9.93 (s, 1H, HO-4'), 8.15 (s, 1H, H-7'), 7.51 (d, J = 8.8 Hz, 2H, H-2' and H- 6'), 7.25 (d, J = 8.4 Hz, 1H, H-6), 6.81 (d, J = 8.4 Hz, 2H, H-3' and H-5'), 6.26 (dd, J = 8.4, 2.4 Hz, 1H, H-5), 6.20 (d, J = 2.4 Hz, 1H, H-3), 2.13 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 171.8 (C-7), 165.3 (C-2), 163.2 (C-4), 159.8 (C-4'), 153.1 (C-7'), 132.9 (C-6), 129.5 (C-2' and C-6'), 129.1 (C-1'), 118.1 (C-3' and C-5'), 109.9 (C-5), 108.2 (C-1), 106.4 (C-3), 15.6 (C-8); EIMS (m/z): 270 [M]+, 120 [C7H6NO]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 93 [C6H5O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2-nitrobenzylidene)hydrazone (4h)

Yellowish brown amorphous solid; Yield: 75 %; M.P.: 208-210 C; Mol. formula: C15H13N3O4; Mol. mass: 299 gmol-1; IR (KBr, max/cm-1): 3262 (O- H), 3028 (Ar C-H), 1665 (C=N), 1602 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.41 (s, 1H, H- 7'), 8.03 (d, J = 8.0 Hz, 1H, H-6'), 7.94 (d, J = 7.8 Hz, 1H, H-3'), 7.67-7.61 (m, 2H, H-4' and H-5'), 7.26 (d, J = 8.8 Hz, 1H, H-6), 6.27 (dd, J = 8.0, 2.0 Hz, 1H, H-5), 6.22 (d, J = 2.0 Hz, 1H, H-3), 2.14 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 174.4 (C-7), 165.3 (C-2), 163.6 (C-4), 152.6 (C-7'), 148.6 (C-2'), 132.8 (C-6), 133.6 (C-3'), 130.4 (C-4'), 126.7 (C-6'), 125.2 (C-1'), 124.5 (C-5'), 109.2 (C-5), 108.4 (C-1), 106.8 (C-3), 15.4 (C-8); EIMS (m/z): 299 [M]+, 149 [C7H5N2O2]+, 122 [C6H4NO2]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(3-nitrobenzylidene)hydrazone (4i)

Yellow amorphous solid; Yield: 77 %; M.P.: 216-218 C; Mol. formula: C15H13N3O4; Mol. mass: 299 gmol-1; IR (KBr, max/cm-1): 3258 (O-H), 3021 (Ar C-H), 1662 (C=N), 1603 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 8.71 (s, 1H, H-2'), 8.63 (s, 1H, H-7'), 8.32 (dd, J = 8.4, 1.6 Hz, 1H, H- 4'), 8.24 (d, J = 7.6 Hz, 1H, H-6'), 7.72 (t, J = 8.0 Hz, 1H, H-5'), 7.56 (d, J = 8.8 Hz, 1H, H-6), 6.38 (dd, J = 8.8, 2.4 Hz, 1H, H-5), 6.30 (d, J = 2.0 Hz, 1H, H- 3), 2.66 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 172.4 (C-7), 164.6 (C-2), 163.7 (C-4), 153.8 (C-7'), 149.5 (C-3'), 136.4 (C-1'), 132.6 (C-6), 129.3 (C-6'), 127.6 (C-5'), 125.2 (C-4'), 122.6 (C-2'), 109.6 (C-5), 108.3 (C-1), 106.7 (C-3), 15.2 (C-8); EIMS (m/z): 299 [M]+, 149 [C7H5N2O2]+, 122 [C6 H4 NO2 ]+, 109 [C6 H5 O2 ]+, 108 [C6 H4 O2 ]+, 83 [C4 H3 O2 ]+, 80 [C5 H4 O]+, 67 [C4 H3 O]+, 51 [C4 H3 ]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(4-nitrobenzylidene)hydrazone (4j)

Brownish red amorphous solid; Yield: 82 %; M.P.: 218-220 C; Mol. formula: C15H13N3O4; Mol. mass: 299 gmol-1; IR (KBr, max/cm-1): 3267 (O-H), 3026 (Ar C-H), 1664 (C=N), 1605 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.34 (s, 1H, H- 7'), 8.26 (d, J = 8.4 Hz, 2H, H-2' and H-6'), 7.97 (d, J = 8.4 Hz, 2H, H-3' and H-5'), 7.25 (d, J = 8.4 Hz, 1H, H-6), 6.26 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.23 (d, J = 2.0 Hz, 1H, H-3), 2.13 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 171.3 (C-7), 165.4 (C-2), 163.3 (C-4), 153.4 (C-7'), 147.7 (C-4'), 139.3 (C-1'), 132.6 (C-6), 127.8 (C-2' and C-6'), 125.5 (C-3' and C-5'), 109.8 (C-5), 108.5 (C-1), 106.3 (C-3), 15.4 (C-8); EIMS (m/z): 299 [M]+, 149 [C7H5N2O2]+, 122 [C6H4NO2]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(4-(dimethylamino)benzylidene)hydrazone (4k)

Reddish brown amorphous solid; Yield: 81 %; M.P.: 186-188 C; Mol. formula: C17H19N3O2; Mol. mass: 297 gmol-1; IR (KBr, max/cm-1): 3263 (O- H), 3020 (Ar C-H), 1660 (C=N), 1608 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.05 (s, 1H, H- 7'), 7.45 (d, J = 8.4 Hz, 2H, H-2' and H-6'), 7.22 (d, J = 8.4 Hz, 1H, H-6), 6.67 (d, J = 8.8 Hz, 2H, H-3' and H-5'), 6.26 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.21 (d, J = 2.4 Hz, 1H, H-3), 3.02 (s, 6H, CH3-8' and CH3-9'), 2.14 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 171.4 (C-7), 165.3 (C-2), 163.8 (C-4), 155.9 (C-4'), 153.6 (C-7'), 132.5 (C-6), 128.3 (C-2' and C-6'), 127.4 (C-1'), 115.6 (C-3' and C-5'), 109.6 (C-5), 108.7 (C-1), 106.4 (C-3), 41.3 (C-8' and C-9'), 15.5 (C-8); EIMS (m/z): 297 [M]+, 147 [C9H11N2]+, 120 [C8H10N]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(4-(diethylamino)benzylidene)hydrazone (4l)

Brownish yellow amorphous solid; Yield: 83 %; M.P.: 190-192 C; Mol. formula: C19H23N3O2; Mol. mass: 325 gmol-1; IR (KBr, max/cm-1): 3269 (O- H), 3024 (Ar C-H), 1663 (C=N), 1607 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.06 (s, 1H, H- 7'), 7.46 (d, J = 8.4 Hz, 2H, H-2' and H-6'), 7.21 (d, J = 8.4 Hz, 1H, H-6), 6.67 (d, J = 8.4 Hz, 2H, H-3' and H-5'), 6.27 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.23 (d, J = 2.0 Hz, 1H, H-3), 3.38 (q, J = 7.2 Hz, 4H, H-8' and H-10'), 1.11 (t, J = 7.2 Hz, 6H, CH3-9' and CH3-11'), 2.15 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 171.8 (C-7), 165.5 (C-2), 163.4 (C-4), 155.7 (C-4'), 154.9 (C-7'), 132.8 (C-6), 128.4 (C-2' and C-6'), 127.2 (C-1'), 115.3 (C-3' and C-5'), 109.9 (C-5), 108.6 (C-1), 106.5 (C-3), 42.5 (C-8' and C-10'), 15.2 (C-8), 12.7 (C-9' and C-11'); EIMS (m/z): 325 [M]+, 175 [C11H15N2]+, 148 [C10H14N]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2,3-dimethoxybenzylidene)hydrazone (4m)

Yellow amorphous solid; Yield: 81 %; M.P.: 168-170 C; Mol. formula: C17H18N2O4; Mol. mass: 314 gmol-1; IR (KBr, max/cm-1): 3263 (O-H), 3021 (Ar C-H), 1664 (C=N), 1606 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 8.34 (s, 1H, H-7'), 7.41 (dd, J = 7.6, 2.8 Hz, 1H, H-6'), 7.25 (d, J = 8.8 Hz, 1H, H-6), 7.13 (dd, J = 8.8, 2.8 Hz, 1H, H-4'), 7.06 (t, J = 7.6 Hz, 1H, H-5'), 6.25 (dd, J = 8.8, 2.4 Hz, 1H, H-5), 6.22 (d, J = 2.4 Hz, 1H, H-3), 3.84 (s, 3H, CH3-9'), 3.77 (s, 3H, CH3-8'), 2.15 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 172.7 (C-7), 164.5 (C-2), 163.6 (C-4), 153.9 (C-7'), 150.1 (C-3'), 148.8 (C-2'), 132.8 (C-6), 124.2 (C-1'), 122.3 (C-6'), 117.3 (C-4'), 115.2 (C-5'), 109.4 (C-5), 108.7 (C-1), 106.1 (C-3), 61.2 (C-8'), 55.7 (C-9'), 15.3 (C-8); EIMS (m/z): 314 [M]+, 164 [C9H10NO2]+, 137 [C8H9O2]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2,4-dimethoxybenzylidene)hydrazone (4n)

Dirty yellow amorphous solid; Yield: 84 %; M.P.: 178-180 C; Mol. formula: C17H18N2O4; Mol. mass: 314 gmol-1; IR (KBr, max/cm-1): 3269 (O-H), 3025 (Ar C-H), 1660 (C=N), 1601 (Ar C=C); 1H- NMR (400 MHz, MeOD, d/ppm): 8.26 (s, 1H, H-7'), 7.72 (d, J = 8.4 Hz, 1H, H-6'), 7.23 (d, J = 8.4 Hz, 1H, H-6), 6.61 (d, J = 2.4 Hz, 1H, H-3'), 6.56 (dd, J = 7.6, 2.4 Hz, 1H, H-5'), 6.23 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.21 (d, J = 2.0 Hz, 1H, H-3), 3.82 (s, 3H, CH3-8'), 3.81 (s, 3H, CH3-9'), 2.13 (s, 3H, CH3-8); 13C-NMR (100 MHz, MeOD, d/ppm): 172.4 (C-7), 164.3 (C-2), 163.8 (C-4), 160.1 (C-4'), 158.3 (C-2'), 153.5 (C-7'), 132.5 (C-6), 127.4 (C-6'), 118.5 (C-1'), 109.8 (C-5'), 109.4 (C-5), 108.3 (C-1), 106.5 (C-3), 100.7 (C-3'), 56.3 (C-8'), 55.3 (C-9'), 15.1 (C-8); EIMS (m/z): 314 [M]+, 164 [C9H10NO2]+, 137 [C8H9O2]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2,5-dimethoxybenzylidene)hydrazone (4o)

Bright brownish yellow amorphous solid; Yield: 80 %; M.P.: 198-200 C; Mol. formula: C17H18N2O4; Mol. mass: 314 gmol-1; IR (KBr, max/cm-1): 3266 (O-H), 3027 (Ar C-H), 1663 (C=N), 1609 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 8.34 (s, 1H, H-7'), 7.32 (d, J = 8.4 Hz, 1H, H- 4'), 7.28 (d, J = 8.0 Hz, 1H, H-6), 7.06 (d, J = 7.6 Hz, 1H, H-3'), 6.98 (d, J = 3.6 Hz, 1H, H-6'), 6.21 (dd, J = 8.4, 2.4 Hz, 1H, H-5), 6.19 (d, J = 2.0 Hz, 1H, H-3), 3.81 (s, 3H, CH3-9'), 3.73 (s, 3H, CH3-8'), 2.14 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 172.8 (C-7), 164.4 (C-2), 163.1 (C-4), 153.8 (C-7'), 149.8 (C-5'), 148.1 (C-2'), 132.7 (C-6), 128.4 (C-1'), 120.1 (C-4'), 115.7 (C-3'), 113.9 (C-6'), 109.9 (C-5), 108.4 (C-1), 106.2 (C-3), 56.5 (C-9'), 55.2 (C- 8'), 15.3 (C-8); EIMS (m/z): 314 [M]+, 164 [C9H10NO2]+, 137 [C8H9O2]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(3,4-dimethoxybenzylidene)hydrazone (4p)

Yellow amorphous solid; Yield: 82 %; M.P.: 172-174 C; Mol. formula: C17H18N2O4; Mol. mass: 314 gmol-1; IR (KBr, max/cm-1): 3269 (O-H), 3023 (Ar C-H), 1662 (C=N), 1607 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 8.41 (s, 1H, H-7'), 7.54 (d, J = 1.6 Hz, 1H, H-2'), 7.51 (d, J = 8.8 Hz, 1H, H-6), 7.36 (dd, J = 8.4, 1.6 Hz, 1H, H-6'), 7.03 (d, J = 8.4 Hz, 1H, H-5'), 6.36 (dd, J = 8.8, 2.4 Hz, 1H, H-5), 6.29 (d, J = 2.4 Hz, 1H, H-3), 3.89 (s, 3H, CH3-8'), 3.87 (s, 3H, CH3-9'), 2.62 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 172.9 (C- 7), 164.5 (C-2), 163.2 (C-4), 155.4 (C-3'), 154.0 (C- 4'), 153.3 (C-7'), 132.8 (C-6), 127.2 (C-1'), 123.6 (C- 6'), 113.8 (C-5'), 109.4 (C-5), 108.1 (C-1), 107.2 (C- 2'), 106.3 (C-3), 56.3 (C-8'), 55.6 (C-9'), 15.4 (C-8); EIMS (m/z): 314 [M]+, 164 [C9H10NO2]+, 137 [C8H9O2]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(4-methoxybenzylidene)hydrazone (4q)

Dark yellow amorphous solid; Yield: 79 %; M.P.: 226-228 C; Mol. formula: C16H16N2O3; Mol. mass: 284 gmol-1; IR (KBr, max/cm-1): 3261 (O-H), 3032 (Ar C-H), 1659 (C=N), 1612 (Ar C=C); 1H- NMR (400 MHz, CD3OD, d in ppm): 8.14 (s, 1H, H- 7'), 7.81 (d, J = 8.4 Hz, 2H, H-2' and H-6'), 7.26 (d, J = 8.4 Hz, 1H, H-6), 6.53 (d, J = 8.4 Hz, 2H, H-3' and H-5'), 6.27 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.21 (d, J = 2.0 Hz, 1H, H-3), 3.81 (s, 3H, CH3-8'), 2.14 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 171.5 (C-7), 165.8 (C-2), 163.4 (C-4), 159.7 (C-4'), 153.4 (C-7'), 132.6 (C-6), 129.3 (C-1'), 126.5 (C-2' and C-6'), 118.7 (C-3' and C-5'), 109.7 (C-5), 108.4 (C-1), 106.3 (C-3), 57.5 (C-8'), 15.4 (C-8); EIMS (m/z): 284 [M]+, 134 [C8H8NO]+, 109 [C6H5O2]+, 108 [C6H4O2]+, 107 [C7H7O]+, 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2,4- dichlorobenzylidene)hydrazone (4r)

Light brownish yellow amorphous solid; Yield: 80 %; M.P.: 212-214 C; Mol. formula: C15H12Cl2N2O2; Mol. mass: 322 gmol-1; IR (KBr, max/cm-1): 3259 (O-H), 3032 (Ar C-H), 1665 (C=N), 1604 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 8.74 (s, 1H, H-7'), 7.57 (d, J = 8.4 Hz, 1H, H- 6), 7.54 (d, J = 8.0 Hz, 1H, H-6'), 7.47 (dd, J = 8.0, 2.0 Hz, 1H, H-5'), 7.32 (d, J = 2.0 Hz, 1H, H-3'), 6.37 (dd, J = 8.4, 2.4 Hz, 1H, H-5), 6.30 (d, J = 2.4 Hz, 1H, H-3), 2.60 (s, 3H, CH3-8); 13C-NMR (100 MHz, CD3OD, d in ppm): 172.6 (C-7), 164.8 (C-2), 163.1 (C-4), 153.3 (C-7'), 136.4 (C-4'), 132.6 (C-6), 130.4 (C-2'), 129.5 (C-1'), 128.3 (C-3'), 125.4 (C-6'), 122.9 (C-5'), 109.3 (C-5), 108.6 (C-1), 106.5 (C-3), 15.2 (C-8); EIMS (m/z): 326 [M + 4] , 324 [M + 2] , 322 [M] , 172 [C7H4Cl2N] , 145 [C6H3Cl2] , 109 [C6H5O2] , 108 [C6H4O2] , 83 [C4H3O2] , 80 [C5H4O] , 67 [C4H3O] , 51 [C4H3].

1-(2,4-Dihydroxyphenyl)-1-ethanone N'-(2,6-dichlorobenzylidene)hydrazone (4s)

Light brownish yellow amorphous solid; Yield: 83 %; M.P.: 196-198 C; Mol. formula: C15H12Cl2N2O2; Mol. mass: 322 gmol -1; IR (KBr, max/cm): 3265 (O-H), 3035 (Ar C-H), 1657 (C=N), 1611 (Ar C=C); 1H-NMR (400 MHz, CD3OD, d in ppm): 8.73 (s, 1H, H-7'), 7.56 (d, J = 8.4 Hz, 1H, H- 6), 7.50 (d, J = 7.6 Hz, 2H, H-3' and H-5'), 7.39 (dt, J = 8.8, 1.6 Hz, 1H, H-4'), 6.38 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.32 (d, J = 2.4 Hz, 1H, H-3), 2.61 (s, 3H, CH3-8); C-NMR (100 MHz, CD3OD, d in ppm): 172.2 (C-7), 164.3 (C-2), 163.2 (C-4), 153.1 (C-7'), 132.9 (C-6), 130.3 (C-2' and C-6'), 128.7 (C-1'), 126.1 (C-4'), 124.8 (C-3' and C-5'), 109.5 (C-5), 108.8 (C-1), 106.1 (C-3), 15.7 (C-8); EIMS (m/z): 326 [M + 4]+, 324 [M + 2] , 322 [M] , 172 [C7H4Cl2N] , 145 [C6H3Cl2] , 109 [C6H5O2] , 108 [C6H4O2] , 83 [C4H3O2]+, 80 [C5H4O]+, 67 [C4H3O]+, 51 [C4H3]+.

Enzyme Inhibition Assays

Butyrylcholinesterase (BChE) Assay

The BChE inhibition study was performed according to the reported method [13-17] with slight modifications. 100 u L reaction mixture containing 60 u L Na2HPO4 buffer (with conc. of 50 mM and pH 7.7), 10 u L test compound (with conc. of 0.5 mM well-1) and 10 u L enzyme of conc. 0.005 unit well-1 was prepared. All contents were immixed and pre- read at a wavelength of 405 nm. Pre-incubation of the contents for 10 min at 37 C was performed and the initiation of the reaction was done through 10 u L of conc. 0.5 mM well-1 substrate (butyrylthiocholine chloride) followed by 10 u L of 5,5'-dithiobis-(2- nitrobenzoic acid) (DTNB, conc. 0.5 mM well-1). After incubation of 15 min at 37 C, absorbance at 405 nm was measured by 96-well plate reader (Synergy HT, Biotek, USA). All the observations were carried out in triplicate with their respective controls. Eserine of conc. 0.5 mM well-1 was applied as a positive control. The results were calculated as per formula.

(Equation)

where Control is the absorbance in the presence of reference and Test is the absorbance in the presence of the test compound. IC50 values were calculated using EZ-Fit Enzyme kinetics software (Perrella Scientific Inc. Amherst, USA). IC50 values were determined by serial dilution of the compounds from 0.5 mM to 0.25, 0.125, 0.0625, 0.03125, 0.015625 mM. IC50 value was calculated from the graph, the concentration at which the enzyme inhibition was 50%. Values are mean of 3 independent experiments.

a-Glucosidase Assay

The a-glucosidase inhibition activity was performed according to the slightly modified method [18, 19]. Total volume of the reaction mixture was made 100 u L by 70 u L phosphate buffer saline (50 mM, pH 6.8), 10 u L test compound (0.5 mM) and 10 u L enzyme (0.057 unitswell-1). The contents were mixed, preincubated for 10 min at 37 C and pre-read at 400 nm. The reaction was initiated by the addition of 10 u L of substrate (0.5 mM, p- nitrophenylglucopyranoside). Acarbose was used as positive control. After 30 min of incubation at 37 C, absorbance was measured at 400 nm using Synergy HT microplate reader. All experiments were carried out in duplicates. The percentage inhibition and IC50 values were calculated by the same method as mentioned for butyryl cholinesterase assay.

Lipoxygenase Assay

Lipoxygenase (LOX) activity was assayed according to the method [13-17] with a little variations. 200 u L lipoxygenase assay having 150 u L sodium phosphate buffer (with conc. 100 mM and pH 8.0), 10 u L compound to be tested and 15 u L purified lipoxygenase enzyme (with conc. 600 units well-1) was prepared. After mixing, pre-reading at 234 nm and pre-incubation for 10 min at 25 C (room temperature), 25 u L substrate solution was used for initiation of reaction. The results were based on the change in absorbance, observed after 6 min at 234 nm using 96-well plate reader (Synergy HT, Biotek, USA). Performance of reaction was done in three- folds. The positive and negative controls were included in the assay. Baicalein (0.5 mM well-1) was used as a positive control. The percentage inhibition and IC50 values were calculated by the same method as mentioned for butyryl cholinesterase assay.

Statistical Analysis

Each result was expressed as mean SEM of three experiments after statistical analysis on ME 2010.

Results and Discussion

Schiff bases, 4a-s, have been synthesized from 2,4-dihydroxyacetophenone (1) in two steps in reasonable amounts as shown in Scheme-1. The respective details of appropriate procedures accompanied by spectral data are given in experimental section. The compounds were analyzed for anti-enzymatic activity against butyrylcholinesterase, a-glucosidase and lipoxygenase enzymes and were found to be notable inhibitors of butyrylcholinesterase enzyme.

Chemistry

The structure of compound, 4a having molecular formula as C15H14N2O2 and molecular ion peak at m/z 254, was established by mass and proton NMR spectroscopic data. The prominent stretching frequencies in IR spectrum are given in experimental section. The distinguished peaks in mass spectrum of benzenmethanimine cation originated at m/z 104 and 4-(1-iminoethyl)-1,3-benzenediol cation at m/z 150. The other eminent fragments are sketched in Fig. 1. Four signals resonated in the proton NMR spectrum for 1-(2,4-dihydroxyphenyl)-1-ethanone at d 7.25 (d, J = 8.4 Hz, 1H, H-6), 6.27 (dd, J = 8.4, 2.0 Hz, 1H, H-5), 6.23 (d, J = 2.0 Hz, 1H, H-3) and 2.14 (s, 3H, CH3-8); and three signals for benzylidene ring at d 8.03 (s, 1H, H-7'), 7.94 (dd, J = 7.6, 1.6 Hz, 2H, H-2' and H-6') and 7.74-7.69 (m, 3H, H-3' to H-5').

The BB and DEPT C-NMR spectra demonstrated 13 signals for 5 quaternary carbons, 9 methine carbons and 1 methyl carbon. 1-(2,4-Dihydroxyphenyl)-1-ethanone carbons resonated at d 171.3 (C-7), 165.8 (C-2), 163.6 (C-4), 132.4 (C-6), 109.9 (C-5), 108.4 (C-1), 106.1 (C-3) and 15.3 (C-8); and benzylidene ring carbons resonated at d 153.4 (C-7'), 139.2 (C-1'), 130.5 (C-3' and C-5'), 128.7 (C-4') and 124.6 (C-2' and C-6'). Thus 4a was named, 1-(2,4-dihydroxyphenyl)-1-ethanone N'-benzylidenehydrazone. The structures and names of other synthesized molecules were also elucidated in a similar way.

Anti-enzymatic activity (in vitro)

The IC50 values along with inhibition (%) against butyrylcholinesterase (BChE), a-glucosidase and lipoxygenase enzymes are presented in Table-1. Most of the molecules exhibited better inhibition results against butyrylcholinesterase (BChE) enzyme and a small number of molecules were active against the remaining two enzymes. All the results were calculated for 0.5 mM concentration of each molecule.

(Equations)

Scheme 1: Synthesis of 1-(2,4-dihydroxyphenyl)-1-ethanone N'-substituted hydrazone (4a-s).

###Com.###R1###R2###R3###R4###R5###Com.###R1###R2###R3###R4###R5

###4a###H###H###H###H###H###4k###H###H###N(CH3)2###H###H

###4b###CH3###H###H###H###H###4l###H###H###N(C2H5)2###H###H

###4c###H###CH3###H###H###H###4m###OCH3###OCH3###H###H###H

###4d###H###H###CH3###H###H###4n###OCH3###H###OCH3###H###H

###4e###OH###H###H###H###H###4o###OCH3###H###H###OCH3###H

###4f###H###OH###H###H###H###4p###H###OCH3###OCH3###H###H

###4g###H###H###OH###H###H###4q###H###H###OCH3###H###H

###4h###NO2###H###H###H###H###4r###Cl###H###Cl###H###H

###4i###H###NO2###H###H###H###4s###Cl###H###H###H###Cl

###4j###H###H###NO2###H###H

Table-1: Anti-enzymatic analysis of Butyrylcholinesterase, a-Glucosidase and Lipoxygenase enzymes.

###Butyryl cholinesterase###a-Glucosidase###Lipoxygenase

###Compd.###Inhibition (%)###IC50###Inhibition (%)###IC50###Inhibition (%)###IC50

###at 0.5 mM###aM###at 0.5 mM###uM###at 0.25 mM###uM

###4a###96.922.15###187.131.64###16.231.23###-###4.780.55###-

###4b###97.281.53###27.110.96###5.281.29###-###12.980.96###-

###4c###98.921.11###34.150.78###97.641.27###279.420.83###27.981.17###-

###4d###35.140.35###-###15.621.09###-###41.481.15###-

###4e###88.631.64###132.861.12###4.220.21###-###45.491.13###-

###4f###97.741.15###39.820.85###5.411.29###-###24.391.05###-

###4g###71.471.58###181.941.15###17.621.12###-###24.871.11###-

###4h###96.921.53###165.741.17###88.231.78###147.721.05###97.931.85###157.641.03

###4i###93.311.13###39.280.68###18.911.14###-###54.961.77###216.671.05

###4j###58.391.84###388.521.33###98.271.54###112.210.97###23.751.02###-

###4k###51.571.57###476.381.24###4.120.54###-###27.180.86###-

###4l###98.750.95###26.120.38###113.251.12###164.230.58###57.891.94###233.751.37

###4m###48.161.57###435.751.14###71.281.18###438.810.55###57.841.39###182.751.09

###4n###71.911.42###289.351.08###47.271.38###-###87.891.14###104.750.95

###4o###9.910.56###-###12.541.11###-###15.680.83###-

###4p###42.360.74###-###20.871.29###-###7.790.33###-

###4q###59.631.96###411.951.58###11.230.32###-###13.170.54###-

###4r###96.380.79###13.570.25###21.881.25###-###36.741.02###-

###4s###98.920.68###17.640.37###113.221.37###135.920.76###14.690.64###-

###Control###82.821.09a###0.850.0001a###92.230.14b###38.250.12b###93.791.27c###22.401.30c

Against butyrylcholinesterase enzyme, the whole series remained active except three compounds, that is, 4d, 4o and 4p. The most active molecules among the series were 4b, 4c, 4f, 4i, 4l, 4r and 4s with IC50 values (u M) of 27.11 0.96, 34.15 0.78, 39.82 0.85, 39.28 0.68, 26.12 0.38, 13.57 0.25 and 17.64 0.37, respectively, relative to 0.85 0.0001 of Eserine, the reference standard. The remaining molecules executed moderately good inhibition potential. The order of all the active molecules was observed to be as 4r > 4s > 4l > 4b > 4c > 4i > 4f > 4e > 4h > 4g > 4a > 4n > 4j > 4q > 4m > 4k. The best activity of 4r and 4s may be attributed because of halogenated aromatic ring fitting well to the active site and showing a number of interactions with amino acid residues in the binding site of the enzyme.

The other two enzymes were moderately inhibited by the synthesized molecules. Only 4c, 4h, 4j, 4l, 4m and 4s remained efficient against a-glucosidase in the order of 4j > 4s > 4h > 4l > 4c > 4m. The molecule 4j exhibited IC50 value of 112.21 0.97 u M relative to 38.25 0.12 u M of Acarbose, the reference. The lipoxygenase enzyme was also inhibited by a few compounds in the relative order of 4n > 4h > 4m > 4i > 4l. The most active compound presented IC50 of 104.75 0.95 u M relative to 22.40 1.30 u M of reference, Baicalein.

Conclusion

The molecules were synthesized benignantly and characterized efficiently by spectral data elucidated from IR, EI-MS, 1H-NMR and 13C-NMR. The enzyme inhibition results, with given IC50 values, rendered this class of compounds as valuable inhibitors of butyrylcholinesterase (BChE) enzyme. As BChE is known to involve in Alzheimer's disease, so these molecules might be considered as valuable entrants for Alzheimer's disease.

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Author:Abbasi, Muhammad Athar; Niazi, Sikander Khan; Rehman, Aziz-Ur-; Siddiqui, Sabahat Zahra; Hussain, Gh
Publication:Journal of the Chemical Society of Pakistan
Article Type:Report
Date:Feb 29, 2016
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