SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NEW PYRAZOLE DERIVATIVES
HTML Full TextSYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NEW PYRAZOLE DERIVATIVES
Mohamed A. Hamed 2, Ahmed A. El Gokha1, Ramzy Essam R. Abdelwahed 1, Asem A. Mohamed 3, Abdel Moneim EL-Torgoman 1 and Ibrahim El-Tantawy El Sayed *1
Chemistry Department 1, Faculty of Science, El-Menoufeia University, Shebin El-Kom, Egypt.
Chemistry Department 2, Faculty of Science, Tanta University, Tanta, Egypt.
Department of Chemistry of Natural and Microbial Products 3, National Research Center, Elbehosst., Dokki, Cairo, Egypt.
ABSTRACT: The synthesis of a novel of pyrazole derivatives was achieved by condensation of acetyl furan with phenyl hydrazine to give hydrazone (1) On the other hand, cyclization of α, β-unsaturated ketone. Using Vilsmeier reagent by DMF (dimethylformamid) and POCl3 Phosphorusoxychloride) to give compound (2). The chemical structures of allnew compounds were established by IR, ¹HNMR, and mass spectra data. All the synthesized compounds were screened for in vitro antibacterial activity and most of them showed potency against both gram positive and gram negative bacteria. Compounds 4-(α-benzoyl aminoacrylic acid) – 3 - Furayl-1-phenylpyrazol, 4 - (α-benzoylaminomethylacrylate)-3-Furayl-1-phenylpyrazol, 4- (2-4-dinitrophenylhydrazone)-3-Furayl-1-phenylpyrazole showed the highest antibacterial activity against Bacillus subtilis strain with minium inhibition zone 19 mm.
Keywords: |
Acetylfuran, Phenylhydrazine, Vilsmeier-Haack Reaction,
Antimicrobial activity
INTRODUCTION: Pyrazole symbolizes a class of simple aromatic ring organic compounds of the heterocyclic series which is a 5-membered ring skeleton composed of three carbon and two nitrogen atoms. Ludwig Knorr was the first who coined the term pyrazole in 1883. In 1959, the first natural pyrazole, 1-pyrazolyl-alanine, was isolated from seeds of watermelons 1-2. A bulk of literature is available to show the biological versatility such as anti-inflammatory 3, antibacterial 4-5, anti-convulsant 6, anticancer 7-8, anti-depressant 9, anti-hyperglycemic 10, antiviral 11, antipyretic 12, antioxidant 13, ant tubercular 14, fungicides 15, and analgesic activities 16.
These pyrazoles have also found applications in Transition-metal chemistry as an analytical reagent 17. Pyrazoles are weak mono-acidic-bases, formatting with mineral acid salts which dissociate in a vacuum and hydrolyse in water.
The ring system is more stable and less reactive than that of pyrrole. N-Phenyl group being replaced by hydrogen, although C-phenyl groups (unless aminated or hydroxylated) There are number of attempts to accomplish their separation through ions formed by addition or loss a proton, or as a result of the association, which is indicated by cryoscopic measurements and by the higher boiling point of isomer sun substituted nitrogen18.
MATERIALS:
Determinations of melting points were performed in open glass capillaries using electro thermal BUCHI (B-540) hot storage melting-point apparatus and are uncorrected. Infra-red (IR) spectra were recorded on a Shimadzu 435 Spectrometer, using KBr discs and values were represented in cm-1 at the Micro analytical Center, Cairo University. (MS) Mass spectra were run on Shimadzu QP-2010 spectrometer and Mass spectra were run on Hewlett Packard 5988 spectrometer at the Micro analytical Center, Cairo University, Egypt. 1HNMRspectrawas recorded on Bruker (300MHz) FT-NMR spectrometer using DMSO and the chemical shifts are given in δ (ppm) using tetramethylsilane (TMS) as an internal standard. Splitting patterns were designated as follows: s: singlet; d: doublet and m: multiplet.
The biological activity analysis was carried out at, Division of Pharmaceutical Industries, National Research Center, Cairo, Egypt. the compounds was made by thin layer chromatography (TLC) on silica gel-precoated aluminum sheets and the spots were detected by the aid of iodine vapour and by exposure to UV lamp at λ254 nm for few seconds. Starting materials, MeOH, DMF, POCl3, hexane and diethyl ether were either commercially available as reported in literature.
Synthesis of 1-phenyl-3-Furayl pyrazole-4-carbaldehyde (2):
Mixture of (0.01 mole) of acetyl furan , and (0.01 mole) of phenylhydrazine in 10ml Ethanol was refluxed in water bath for 4 h. the reaction mixture was cooled .the solid formed dried and crystallization from diethyl ether the formed of hydrazones (l) Show the following data; yellow color solid , Yield= 66.9%, MP. =75-73 ºC, and Mixture of 2.0gm (0.01 mole) of (I) Vilsmeier reagent, and 0.73 gm (0.01 mole) of DMF(di methyl form amid), 1.53gm (0.01 mole) of POCl3 (Phosphorusoxychloride) was added drop wise with mechanical stirring for five hour. The reaction mixture was refluxed for six hours at 70-80oC, then hydrolyzed on ice/water mixture, and neutralized by 5% NaOH Solution till pH4, the reaction mixture was cooled. The solid formed was filtered, washed with water, dried and crystallization from isopropanol. Show the following data Mp. 252-3 ºC; Yield: (90.2%), Infra-red spectra of compound (2) show: νC=Oofald.1667.16,νC=N1602.56, νC=C 1510.89, νC-Hof 2 adj.H820.02 and νC-Hof 5 adj.H 731.10 cm-1, 1HNMR (DMSO, 300 MHz) δppm=10.13 (s,1H,CHO), 9.31 (C-H Pyrazole), 6.54– 7.95 (m, 8H,Ar- H ), The mass spectra show the molecular ion peak at m/e = 238 [M]+ ,78 %)The base ion peak at m/e=77 [M]+ (-C8H5N2O,100%),m/e= 209[M]+ (- CHO,15.2 %), m/e=237[M]+(-H,74%), m/e=210[M]+(-CO ,20%).
General method for preparation of compounds 3a, 3b:
Mixture of 0.24gm (0.001 mole) of compound (2), 0.18 gm, (0.001 mole) of benzoyl glycine ,0.12 gm. (0.001 mole) acetyl glycine and 0.04 gm.(0.001 mole) of sodium acetate in 5ml acetic anhydride. Was refluxed for two hours. The reaction mixture was cooled. hydrolyzed on ice/water. The solid formed was filtered, washed with water till pH7, then dried, crystallization from carbon tetrachloride.
Synthesisof 4 - [2' - Phenyl-5'(4'H)-oxazolonyl methylidene]-3-Furayl-l-phenylpyrazole(3a):
Show the following data; MP. =206 -7 ºC Yield= 78.7%, Infra-red spectra of compound (3a) show: νC=O1782.37, νC=C1639, νC=N 1588.49 and νC-O1227.4 cm-1 , 1HNMR (DMSO-300 MHz): δ ppm = 8.1(m,2H,C-HPyrazole),7.94(m,2H,Ph-H),7.87 (m,3H,Ph-H),7.27– 7.64 (m, 5H, Ar-H),7.15 (CH=CH), The mass spectra show the molecular ion peak at m/e = 381 [M]+ ,75 %)The base ion peak at m/e = 77[M]+ (- C17H10N3O3 ,100 %),m/e=337 [M]+(-CO2,30.2%),m/e= 314 [M]+(-C4H3O,15.5%), m/e=222[M]+ (-C9H5NO2 ,4.3%) .
Synthesis of 4-[2' -methyl-5'(4'H)-oxazolony lmethylidene]-3-Furayl-l-phenylpyrazole(3b):
Show the following data; MP. =147-8 ºC Yield= 84.6%, Infra-red spectra of compound (3b) show: νC=O 1720.73, νC=C 1605, νC=N 1518.49 and νC-O 1237.3 cm-1, The mass spectra show the molecular ion peak at m/e = 319 [M]+, 2.1 %) The base ion peak at m/e = 237[M]+ (- C3NO2 ,100 %), m/e=248M]+(-C3H3O2,4.5%), m/e = 222 [M]+ (-C4H3NO2,5.3%),m/e=77[M]+ (-C12H8N3O3,55.3%, m/e=67[M]+ (-C14H10N3O2 ,30.2%).
General method for preparation of compounds 4a, 4b:
Mixture of 0.23gm (0.00065 mole) of compounds (3a, 3b), and 0.026 gm. (0.00065 mole) sodium hydroxide in 25ml ethanol was refluxed for three hours. The solution was concentrated, diluted with 100 ml water and acidified with 2% solution HCL. The solid formed was filtered, washed with water, then dried and crystallization from ethanol.
Synthesis of 4-(α-benzoyl aminoacrylic acid)-3-Furayl-1-phenylpyrazol (4a):
Show the following data; MP. =209-10 ºC Yield= 62.4%, Infra-red spectra of compound (4a) show: ν-NH 3324, νC=OofPh1682νC=Oof acid 1628, νC=N 1576, and νC=C1561.62cm-1, 1HNMR (DMSO-300 MHz): δ ppm = 10.43(C-H acid),8.43 (m,3H,Ph-H),8.1(C-H Pyrazole),7.2– 7.96 (m,5H,Ar-H), The mass spectra show the molecular base ion peak at m/e = 399[M]+ ,100 %), m/e = 382 [M]+(- OH ,35 %),m/e=354 M]+(-COOH,10.6%), m/e = 95 [M]+ C19H14NO3, 7.3%), m/e=77[M]+ (-C17H12N3O4,86%).
Synthesis of 4-(α-acetylaminoacrylic acid)-3-Furayl-1-phenylpyrazol (4b):
Show the following data; MP. =152-3 ºC Yield= 91.2%, Infra-red spectra of compound (4b) show: ν-NH 3324, νC=Oof CH3 1688,νC=Oof acid 1632, νC=N 1580 andνC=C 1565cm-1,The mass spectra show the molecular base ion peak at m/e = 337 [M]+ ,100 %), m/e = 320[M]+ (- OH ,40.5 %), m/e=292 [M]+ (-COOH, 14.3%) , m/e= 279 [M]+(-C2H4NO,7.2%), m/e=77[M]+(- C12H10N3O4 ,73.8%).
Synthesis of 4-(α-benzoylaminomethyl acrylate)-3-Furayl-1-phenylpyrazol (5):
A suspension containing (0.0005 mole) of compound (3a), 0.19 gm. in 25 ml methanol and 0..04gm (0.0005mole) sodium acetate .was refluxed for 30 hours. The solution was concentrated and cooling, the solid formed was filtered, and crystallization from ethanol, Show the following data MP. = 222-3ºC Yield = 82.2%, Infra-red spectra of compound (5) show: ν-NH 3323,νC=OofPh 1761, νC=Oof ester 1720, νC=N 1674, andνC=C 1561cm-1,1HNMR (DMSO-300 MHz): δ ppm = 8.1(C-H Pyrazole) ,7.4– 8.2 (m,5H,Ar-H),6.64 (CH=C), 3.77(s,3H, CH3), The mass spectra show the molecular ion peak at m/e = 413 [M]+ , 9.4 %) The base ion peak at m/e = 95[M]+ (- C20H16NO3 ,100 %), m/e=382 [M]+ (-OCH3, 8.5%), m/e= 308 [M]+ (C7H5O,1.2%), m/e = 222[M]+(-C10H9NO3,4.1%), m/e=67[M]+(-C20H16N3O3,48.2 %).
Synthesis of 4-(α-benzoylaminoacrylic acid hydrazide)-3-Furayl-1-phenylpyrazol (6):
A Mixture of 0.31 gm. (0.0008mole) of compound (3a). And 0.0008 ml (0.0008 moles) of 50% hydrazine hydrates in 20ml ethanol. Was refluxed for eight hours. The solution was concentrated and cooling, the solid formed was filtered, and crystallization from ethanol, Show the following data MP. = 204-5 °C, Yield = 75.6%, Infra-red spectra of compound (6) show: νC-NH 3431, νNH2 3280, νC=O 1668, νC=N 1622 and νC=C 1554 cm-1,1HNMR (DMSO-300 MHz): δ ppm = 8.4(C-H Pyrazole) ,7.2– 8.3 (m, 5H,Ar- H) ,6.54 (CH=C),1.9(-NH2),The mass spectra show the molecular ion peak at m/e = 413 [M]+ ,33 %) The base ion peak at m/e = 77[M]+ (- C17H14N5O3 ,100 %), m/e=397 [M]+ (-NH2, 3.5%) , m/e= 354 [M]+(-CH3N2O ,1.2%), m/e=293 [M]+ (-C7H6NO3, 20%) , m/e=67[M]+(-C19H16N5O2,63%).
Synthesis of α, α—bis ((3-Furayl-1-Phenyl pyrazolyl) -4-methylidene) cyclohexanone: (7)
A mixture of 0.2gm (0.00085 mole) of compound (2),and 0.17 ml. (0.0017 mole) cyclohexanone in 50% aqueous (DMSO) dimethylsulphoxide and 10 ml sodium hydroxide was stirred at 100oC for five hours. After cooling and neutralization with diluted HCL. The solid formed was filtered, washed with water, then dried and crystallization from ethanol, Show the following data MP. = 273-4°C, Yield = 83 %, Infra-red spectra of compound (7) show: νC=C 3055, νC=O 1659and νC=N 1628cm-1, 1HNMR (DMSO-300 MHz): δ ppm = 8.43(s,C-H Pyrazole) ,8.41(D,CH=CH),7.1– 7.42 (m, 5H,Ar-H),1.55 (t,2H,CH2), The mass spectra show the molecular ion peak at m/e = 538 [M]+ ,15.6 %)The base ion peakatm/e=67[M]+(-C30H23N4O2,100%),m/e=510 [M]+(-CO, 23%), m/e=444 [M]+(-C6H6O ,20.6%), m/e=222 [M]+ (-C20H16N2O2, 4%), m/e=95[M]+(-C30H23N2O2,4.3%).
Synthesis of 4-(2-4--dinitrophenylhydrazone)-3-Furayl-1-phenylpyrazole (8):
A mixture of 0.083 gm (0.00085 mole). of concentrated sulphuric acid H2SO4 was added coutiosouly to a suspension of 0.17 gm (0.00085mole) 2.4dinitrophenyl hydrazine(DNP) in 10 ml methanol. The solution was wormed and filtered. And 0.2 gm (0.000085 mole) of compound (2) was added to the filtrate with stirring. The solid formed was filtered, and crystallization from ethanol, Show the following data MP = 281-2 ◦C, Yield = 87.2%, Infra-red Spectra of compound (8) show:ν-NH3230 ,νC=N 1612, νC=C 1524, νC-H of 2 adj.H 815and νC-H of 5 adj.H 724 cm-1, 1HNMR (DMSO-300 MHz):δ ppm = 7.2-8.4 (m,5H, Ar- H), 8.6(CH=N), 7.1 (-NH)The mass spectra show the molecular ion peak at m/e=418[M]+,32.6 %)The base ion peak at m/e = 67 [M]+(- C16H11N6O4 ,100 %), m/e=372 [M]+(-NO2, 76.1%),m/e=326 [M]+(-N2O4,65.3%), m/e=222 [M]+ (-C6H4N4O4,3.2%), m/e=95[M]+(-C16H11N4O4,3.4%).
Synthesis of 4-[(2'-Phenyl-2'-imidazolin-5'-onyl)methylidene]-3-Furayl-l phenylpyrazole(9)
A Mixture of 0.2gm (0.00085 mole) of compound (2), and 0.27 gm. (0.0017 mole) of benzamidine hydrochloride dehydrate and 0.2 gm. (0.0017 mole) of Ethylchloroacetate in 20ml n- propanol . Was refluxed with strring for one hours. The solid formed was filtered, washed with methanol, water, and finally with methanol, then dried and crystallization from n-butanol, Show the following data MP. = 324-5◦C, Yield = 92.8 %, Infra-red spectra of compound (9)νc-NH 3105, νC=O1705,νC=C 1640and νC=C 1640cm-1,1HNMR ( DMSO-300 MHz): δ ppm = 8.43 (s,C-H Pyrazole) ,8.01(-NH),6.98– 7.86 (m, 13H, H aroma), The mass spectra show the molecular ion peak at m/e = 380 [M]+ ,39.2 %)The base ion peak at m/e = 67[M]+ (- C19H13N4O, 100%),m/e=352[M]+(-CO, 5.9%), m/e=248 [M]+(-C8H6NO,13.6%),m/e=222[M]+ (-C9H6N2O, (20.3%), m/e = 95[M]+ (- C19H13N2O, 45.2%).
Synthesis of 4, 3-[(6-Amino-5--cyano-4- -phenyl] -3-Furayl-1-phenylpyrazole (10):
A Mixture of 0.03gm (0.000125 moles) of compound (2), and 0.008 gm. (0.000125 mole) of malononitrile and in 20ml absolute ethanol and few drops of piperidine were refluxed for four hours. After cooling the separated solid was filtered, dried, and crystallization from ethanol, Show the following data MP. = 204-5◦C. Yield = 89.4 %, The spectra of compound (10) show 1HNMR (DMSO-300 MHz): δ ppm = 8.43(s, C-H Pyrazole), 7.86– 7.45 (m, 8H, H aroma), 6.98 (D, CH=CH), The mass spectra show the molecular ion peak at m/e = 286 [M]+ ,16.2 %) The base ion peak at m/e = 67[M]+ (-C13H7N4, 100%), m/e=285[M]+(-H, 33.2%),m/e=260 [M]+(-CN,52.1%),m/e=259[M]+ (-HCN, (13.2%), m/e = 95[M]+ (- C13H7N2,6.2%).
RESULTS AND DISCUSSION:
Substituted phenyl hydrazines were prepared by heating substituted a acetyl furan with different hydrazines in methanol under reflux for 4-5 h. Vilsmeier-Haack reaction of phenyl hydrazines using DMF and POCl3 afforded 1-phenyl-3-Furayl pyrazole-4-carbaldehyde in good yields and in high purity. The structures were confirmed on the basis of IR, 1HNMR and mass spectral data according to scheme(1).
The aldehyde (2) were converted into 4-[2' -Phenyl-5'(4'H)-oxazolonylmethylidene]-3-Furayl-l-phenylpyrazole(3a) and 4-[2' -methyl-5'(4'H)-oxazolonyl methylidene] - 3- Furayl - l-phenyl pyrazole (3b) to react with benzoyl glycine ,acetyl glycine in presence of sodium acetate in 5ml acetic anhydride The structures were confirmed on the basis of IR, 1H NMR and mass spectral data according to scheme (2) and the end product (3a, 3b) to hydrolysis with sodium hydroxide to yield4-(α-benzoyl aminoacrylic acid)-3-Furayl-1-phenyl pyrazol(4a)4-(α-acetylaminoacrylicacid)- 3-Furayl-1-phenylpyrazol(4b)The structures were confirmed on the basis of IR, 1H NMR and M.S. data according to scheme (2).
And the hydrolysis of compound (3a) with sodium acetatetoformed4-(α-benzoylaminomethylacrylate)-3-Furayl-1-phenylpyrazol(5) and react with hydrazine hydrate to formed the 4-(α-benzoylaminoacrylic acid hydrazide) – 3 - Furayl-1-phenylpyrazol(6)The structures were confirmed on the basis of IR, 1HNMR and M.S. data according to scheme (3)
and The aldehyde (2) were converted into α, α--bis((3-Furayl-1-Phenylpyrazolyl) – 4 -methylidene) cyclohexanone(7), 4-(2-4—dinitrophenyl hydra zone) -3-Furayl-1-phenylpyrazole (8) to react with cyclohexano n in 50% aqueous (DMSO) dimethyl sulphoxide , concentratedsulphuricacidH2SO4and .4dinitrophenyl hydrazine(DNP) The structures were confirmed on the basis of IR, 1H NMR and mass spectral data according to scheme (4)
and The aldehyde (2) react with benzamidine hydrochloride dehydrate and Ethylchloroacetate , malononitrile to formed the compounds 4-[(2'-Phenyl-2'-imidazolin-5'-onyl) methylidene]-3-Furayl-l phenylpyrazole(9) 4, 3-[(6-Amino-5--cyano-4- -phenyl]-3-Furayl-1-phenylpyrazole (10) The structures were confirmed on the basis of IR, 1HNMR and mass spectral data according to scheme (5)
A possible mechanism for cyclization along with formylation of pyrazole is outlined in scheme (6). The proposed mechanism is initial electrophilic attack of Vilsmeier-Haack reagent (A) on hydrazone(1) yielded the intermediate (B)which subsequently losses amolecule of HCl to provide intermediate (C). The nucleophilic attack by N-H group initiates the cyclisation and the resulting pyrazole intermediate losses Me2NH to give the more stable pyrazole derivative (D). The pyrazole (D) react with another molecule of V.H. reagent (A) in an electrophilic substitution process giving an minimum salt (E), which is hydrolysed to corresponding 4-formyl pyrazole (2) as depicted in scheme (6), In summary the electrophilic attack of first Vilsmeier –Haack (VH) complex at the probable attacking site of hydrazones results into cyclisation. While electrophilic attack of second (VH) complex forms formyl product after hydrolysis. Finally intra molecular (1,5) hydrogen shift, cyclisation and elimination of NHMe2 to give pyrazole derivative with this series of pyrazole aldehydes in hand.
Antimicrobial screening:
The antibacterial activities of the synthesized compounds were tested against Escherichia coli NRRL B-210 and Pseudomonas NRRL B-23 (Gram -ve bacteria), Bacillus subtilis NRRL B-543 and Staphylococcus aureus NRRL B-313 (Gram +ve bacteria) using nutrient agar medium. The antifungal activity of these compounds was also tested against Candida albicans NRRL Y-477 using Sabouraud dextrose agar medium.
Agar Diffusion Medium:
The synthesized compounds were screened in vitro for their antimicrobial activity against, by agar diffusion method (Cruickshank et al.1975). 0.5 ml suspension of each of the aforementioned microorganisms was added to sterile nutrient agar media at 45°C and the mixture was transferred to sterile Petri dishes and allowed to solidify. Holes of 0.9cm in diameter were made using a cork borer. Amounts of 0.1ml of the synthesized compounds were poured inside the holes. A hole filled with DMSO was also used as control. The plates were left for 1 hour at room temperature as a period of pre-incubation diffusion to minimize the effects to variation in time between the applications of the different solutions. The diameters of the inhibition zone of were measured and compared with that of the standard and the values were tabulated. The same method was carried out using Sabouraud dextrose agar medium on using Candida albicans NRRL Y-477. The plates were then incubated at 30°C for 24 hours and observed for antibacterial activity. The diameters of inhibition zone were measured and compared with that of the standard, the values were tabulated. Ciprofloxacin (50µg/ml) and Fusidic acid (50µg/ml) were used as standard for antibacterial and antifungal activity respectively 19-21. The observed zone of inhibition is presented in Table 1.
TABLE 1: IN VITRO ANTIMICROBIAL ACTIVITY BY AGAR DIFFUSION METHOD OF TESTED COMPOUNDS
Compds. | Microorganism inhibition zone diameter mm (Relative inhibition %) | ||||
Gram +ve bacteria | Gram –ve bacteria | Fungi | |||
BacillusSubtilis | Staphylococcus aureus | Escherichiacoli | Pseudomonas
aeuroginosa |
Candida albicans | |
2 | 13(65) | 13(68.4) | 18(94.7) | 12(66.7) | 13(65) |
3a | 12(60) | 18(94.7) | 17(89.5) | -ve(0) | 12(60) |
3b | 17(85) | 17(89.5) | 18(94.7) | 12(66.7) | 14(70) |
4a | 19(95) | 16(84.2) | 12(63.2) | 13(72.2) | 12(60) |
4b | 14(70) | 14(73.7) | 13(68.4) | 17(94.4) | 13(65) |
5 | 19(95) | 13(68.4) | 12(63.2) | -ve(0) | 18(90) |
6 | 13(65) | 12(63.2) | 12(63.2) | 16(88.9) | 12(60) |
7 | 13(65) | 14(73.7) | 16(84.2) | 14(77.8) | 14(70) |
8 | 19(95) | 18(94.7) | 12(63.2) | 13(72.2) | 17(85) |
9 | 15(75) | 14(73.7) | 13(68.4) | 16(88.9) | 14(70) |
Ciprofloxacin | 20(100) | 19(100) | 19(100) | 18(100) | - |
Fusidic acid | - | - | - | - | 20(100) |
Highly active (+++)= (inhibition zone > 17 mm)
Moderately active (++)=(inhibition zone 12 - 16 mm)
Slightly active (+)= (inhibition zone 8 - 11 mm)
Inactive (-ve) = (inhibition zone < 8 mm)
CONCLUSION: In the present study, our attention was focused on the synthesis and antimicrobial, antifungi evaluation of pyrazol derivatives compound. The antimicrobial activity of compounds 3b,4a, 5,8 indicated Highly activity against Bacillus subtilis (Gram +ve bacteria) and moderate activity to compounds 2,3a,4b, 6,7,9 and the compound 2,3a,3b,7 the Highly activity against against E coli (Gram -ve bacteria) while the compounds 4a,4b,5,6,8,9 moderate activity. And the antifungal activity the compounds 5,8 is highly activity against Candida albicans while the compunds 2,3a,3b,4a,4b,6,7,9 is moderate activity.
ACKNOWLEDGEMENT: The authors are thankful to the Department of organic chemistry of Menoufia University, Egypt for providing literature survey facility to carry out the work.
REFERNECES:
- Noe, F. F. and L. Fowden 1959. Alpha-Amino-beta-(pyrazolyl-N) propionic acid: a new amino-acid from Citrullus vulgaris (water melon). Nature 184: 69–70.
- Eicher T. and Hauptmann, S. 2003. The Chemistry of heterocycles: structure, reactions, syntheses, and applications, Wiley-VCH. Edition 2nd.
- Ragab, F.A., Abdel Gawad, N.M., Georgey, H.H. and Said, M.F. 2013. Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents. Eur. J. Med. Chem. 63: 645–654.
- Damlijanovic, I., Vukicevic, M., Radulovic, N., Palic, R., Ellmerer, E., Ratkovic, Z., Joksovic, M.D. and Vukicevic, R.D. 2009. Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit. Bioorg. Med. Chem. Lett. 19: 1093–1096.
- Desai, N.C., Rajpara, K.M. and Joshi, V.V. 2013.Synthesis of pyrazole encompassing 2-pyridone derivatives as antibacterial agents.Bioorg. Med. Chem. Lett. 23: 2714–2717.
- Amnerkar, N.D. and Bhusari, K.P. 2010. Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole. Eur. J. Med. Chem. 45: 149–159.
- Clapham, K.M., Batsanov, A.S., Bryce, M.R. and Tarbit, B. 2009. Trifluoromethyl-substituted pyridyl and pyrazolylboronic acids and esters: Synthesis and Suzuki–Miyaura cross-coupling reactions. Org. Biomol. Chem. 7: 2155–2161.
- Lv, P.-C., Li, H.-Q., Sun, J., Zhou, Y. and Zhu, H.-L. 2010. Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents. Bioorg. Med. Chem. 18: 4606–4614.
- Ozdemir, Z., Kandilici, H.B., Gumusel, B., Calis, U. and Bilgin, A. 2007. Synthesis and studies on Antidepressant and Anticonvulsant Activities of Some 3-(2-furyl)-pyrazoline Derivatives. Eur. J. Med. Chem. 42: 373–379.
- Gregory, R., Bebernitz, G., Argentieri, B. B., Christine, B., Bork, B., Bryan, F., Burkey, M., Eckhardt, J., Gao, P. K., Robert J., Strohschein, H. F., Schuster M. W. and David D. Xu 2001. The effect of 1,3-diaryl-[1H]-pyrazole-4-acetamides on glucose utilization in ob/ob Mice. J. Med. Chem. 44: 2601–2611.
- Park, H.-J., Lee, K., Park, S.-J., Ahn, B., Lee, J.-C., Cho, H. and Lee, K.-I. 2005. Identification of antitumor activity of pyrazoleoxime ethers. Bioorg. Med. Chem. Lett. 15: 3307–3312.
- Sener, A., Kasim-Sener, M., Bildmci, I., Kasimogullari, R. and Akçamur, Y. 2002. Studies on the reactions of cyclic oxalyl compounds with hydrazines or hydrazones: Synthesis and reactions of4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid. J. Heterocycl. Chem. 39: 869–875.
- Rangaswamy, J., Kumar, H.V., Harini, S.T. and Naik, N. 2012. Synthesis of benzofuran based 1,3,5-substituted pyrazole derivatives: As a new class of potent antioxidants and antimicrobials-A novel accost to amend biocompatibility. Bioorg. Med. Chem. Lett. 22: 4773–4772.
- Pathak, R.B., Chovatia, P.T. and Parekh, H.H. 2012. Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives. Bioorg. Med. Chem. Lett. 22: 5129–5133
- Vicentini, C.B., Romagnoli, C., Andreotti, E. and Mares, D. 2007. Synthetic pyrazole derivatives as growth inhibitors of some phytopathogenic fungi. J. Agric. Food Chem. 55: 10331–10338.
- Vijesh, A.M., Isloor, A.M., Shetty, P., Sundershan, S. and Fun, H.K. 2013. New pyrazole derivatives containing 1,2,4-triazoles and benzoxazoles as potent antimicrobial and analgesic agents. Eur. J. Med. Chem. 62: 410–415.
- Wisniewski, M.Z., Surga, W.J. and Opozda, E.M. 1994. Palladium (II) methylpyrazole complexes. Transition Met. Chem. 19: 353–354.
How to cite this article:
Md. Hamed A, El Gokha AA, Abdelwahed RER, Mohamed AA, EL-Torgoman AM and El-Tantawy El Sayed I: Synthesis and biological evaluation of some new pyrazole derivatives. Int J Pharm Sci Res 2016; 7(11): 4414-21.doi: 10.13040/IJPSR.0975-8232.7(11).4414-21.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
13
4414-21
544
1764
English
IJPSR
Md A. Hamed, Ahmed A. El Gokha, R. Essam R. Abdelwahed, A. A. Mohamed , A. Moneim EL-Torgoman and Ibrahim El-Tantawy El Sayed *
Chemistry Department, Faculty of Science, El-Menoufeia University, Shebin El-Kom, Egypt
ibrahimtantawy@yahoo.co.uk
11 June, 2016
16 August, 2016
28 September, 2016
10.13040/IJPSR.0975-8232.7(11).4414-21
01 November, 2016