Synthesis, Spectroscopy and Electrochemistry of New 3-(5-Aryl-4,5-Dihydro-1H-Pyrazol-3-yl)-4-Hydroxy-2H-Chromene-2-One 4, 5 as a Novel Class of Potential Antibacterial and Antioxidant Derivatives
Author(s)
Abdullah Sulaiman Al-Ayed
ABSTRACT
3-((2E)-3(aryl)prop-2-enoyl)-2H-chromen-2-one 3 was synthesized from 4-hydroxy coumarin by refluxing 3-acetyl-4-hydroxy coumarin with aromatic aldehydes in chloroform in the presence of a catalytic amount of piperidine. 3 was converted to pyrazoles 4, 5 by treatment with hydrazine and phenylhydrazine in toluene, respectively. The structures of the new compounds were confirmed by elemental analysis, IR, and multinuclear/multidimensional NMR spectroscopy (1H, 13C-NMR, NOESY, HMBC) which allowed us to assign the complete network of proton and carbon atoms. All the compounds exhibited one quasireversible redox process. All the newly synthesized compounds were screened for their antibacterial and antioxidant activities. Antimicrobial studies revealed that 3-(5-(2,5-dimethylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-4- hydroxy-2H-chromene-2-one 5c showed significant antibacterial activity against Escherichia coli and Pseudomonas Aeruginosa 27853. Furthermore, 3-(5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene- 2-ones 4, 5 showed antioxidant activities of different extents with respect to individual compounds as well as to the antioxidant methods. The 3-(5-(phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-ones 4a was found to be the most active antioxidant in the series and more active than trolox which makes the investigated complexes a new promising class of antibacterial compounds.
3-((2E)-3(aryl)prop-2-enoyl)-2H-chromen-2-one 3 was synthesized from 4-hydroxy coumarin by refluxing 3-acetyl-4-hydroxy coumarin with aromatic aldehydes in chloroform in the presence of a catalytic amount of piperidine. 3 was converted to pyrazoles 4, 5 by treatment with hydrazine and phenylhydrazine in toluene, respectively. The structures of the new compounds were confirmed by elemental analysis, IR, and multinuclear/multidimensional NMR spectroscopy (1H, 13C-NMR, NOESY, HMBC) which allowed us to assign the complete network of proton and carbon atoms. All the compounds exhibited one quasireversible redox process. All the newly synthesized compounds were screened for their antibacterial and antioxidant activities. Antimicrobial studies revealed that 3-(5-(2,5-dimethylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-4- hydroxy-2H-chromene-2-one 5c showed significant antibacterial activity against Escherichia coli and Pseudomonas Aeruginosa 27853. Furthermore, 3-(5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene- 2-ones 4, 5 showed antioxidant activities of different extents with respect to individual compounds as well as to the antioxidant methods. The 3-(5-(phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromene-2-ones 4a was found to be the most active antioxidant in the series and more active than trolox which makes the investigated complexes a new promising class of antibacterial compounds.
Cite this paper
nullA. Al-Ayed, "Synthesis, Spectroscopy and Electrochemistry of New 3-(5-Aryl-4,5-Dihydro-1H-Pyrazol-3-yl)-4-Hydroxy-2H-Chromene-2-One 4, 5 as a Novel Class of Potential Antibacterial and Antioxidant Derivatives," International Journal of Organic Chemistry, Vol. 1 No. 3, 2011, pp. 87-96. doi: 10.4236/ijoc.2011.13014.
nullA. Al-Ayed, "Synthesis, Spectroscopy and Electrochemistry of New 3-(5-Aryl-4,5-Dihydro-1H-Pyrazol-3-yl)-4-Hydroxy-2H-Chromene-2-One 4, 5 as a Novel Class of Potential Antibacterial and Antioxidant Derivatives," International Journal of Organic Chemistry, Vol. 1 No. 3, 2011, pp. 87-96. doi: 10.4236/ijoc.2011.13014.
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[1] F. Aqil and I. Ahmad, “Rapid and Accurate Species―Specific Detection of Phytophthora Infestans throu- gh Analysis of Its Regions in Its rDNA,” Journal of Microbiology and Biotechnology, Vol. 19, No. 6, 2000, pp. 653-657. [2] A. W. Bauer, W. M. M. Kirby, J. C. Sherris and M. Turch, “Antibiotic Susceptibility Testing by a Standardized Single Disk Method,” American Journal of Clinical Pathology, Vol. 45, No. 5, 1998, pp. 493-496. [3] O. Bruno, A. Ranise, F. Bonadavalli, P. Schenone, M. D’Amico, W. Felipplli, A. Filippelli and F. Rossi, “3,5- Diphenyl-1H-Pyrazole Derivatives. XI. N-Aryl-5(3)- Phenyl-4-(3,5-Diphenyl-1-Pyrazolyl)-3(5)-Pyrazole Ami- nes, 5-Substituted 4,5-Dihydro-3-Phenyl-4-(3,5-Diphenyl -1-Pyrazolyl)-1H-Pyrazoles and 2,6-Disubstituted 1,6-Di- hydro-4-Phenyl-5-(3,5-Diphenyl-1-Pyrazolyl)Pyrimidines with Antipyretic, Anti-Inflammatory and Other Activi- ties,” Farmaco, Vol. 48, No. 4, 1998, pp. 949-966 [4] J. R. Dimmock, S. K. Raghavan, et al., “Antileukemic Evaluation of Some Mannich Bases Derived from 2- Arylidene-1,3-Diketones,” European Journal of Medicinal Chemistry, Vol. 18, No. 4, 1998, pp. 248-254. [5] H. R. Eisenhauer and K. P. Link,“ Studies on 4-Hydroxy- Coumarins. XIII. The Mechanism for the Reaction of 4-Hydroxycoumarin with Aliphatic Acid Chlorides,” Journal of the American Chemical Society, Vol. 75, No. 9, 1953, pp. 2044-2050. doi:10.1021/ja01105a006 [6] A. A. El-Barbary, A. I. Khodair, E. B. Pederson and C. Nielsen, “S-Glucosylated Hydantoins as New Antiviral agents,” Journal of Medicinal Chemistry, Vol. 37, No. 1, 1994, pp. 73-77. doi:10.1021/jm00027a009 [7] E. S. M. El-khawass and A. E. Bistawroos, “Synthesis and Biological Activity of Heterocycles from Chalcone,” Medicinal Chemistry Research, Vol. 17, No. 2-7, 2008, pp. 318-325 [8] H. I. El-Subbagh, S. M. Abu-Zaid, M. A. Mahran, F. A. Badaria, Al-Obaid,” Synthesis and Biological Evaluation of Certain α,β-Unsaturated Ketones and Their Corresponding Fused Pyridines as Antiviral and Cytotoxic Agents,” Journal of Medicinal Chemistry, Vol. 43, No. 15, 2000, pp. 2915-2921. doi:10.1021/jm000038m [9] E. O. Nuzum, P. J. Rosenthal and J. H. Mckerrow, “In Vitro Antimalarial Activity of Chalcones and Their Derivatives,” Journal of Medicinal Chemistry, Vol. 38, No. 26, 1995, pp. 5031-5037. doi:10.1021/jm00026a010 [10] A. Nayak and A. S. Mittra, “4,4-Bis-5-Pyrazolones and Their 4,4-Unsaturated Products for Possible Use as Fungicides,” Journal of the Indian Chemical Society, Vol. 57, 1980, pp. 643-649 [11] N. Marquez, R. Sancho, L. M. Bedoya, J. Alcamy, J. L. Lopez-Perez, A. S. Feliciano, B. L. Fiebich and E. Munoz, “Mesuol, a Natural Occurring 4-Phenylcoumarin, Inhibits HIV-1 Replication by Targeting the NF-κB Pathway,” Antiviral Research, Vol. 66, No. 2-3, 2005, pp. 137-143. doi:10.1016/j.antiviral.2005.02.006 [12] C. Spino, M. Dodier and S. Sotheeswaran, “Anti-HIV Coumarins from Calophyllum Seed Oil,” Bioorganic & Medicinal Chemistry Letters, Vol. 8, No. 24, 1998, pp. 3475-3481. doi:10.1016/S0960-894X(98)00628-3 [13] S. Thaisrivongs, K. D. Watenpaugh, W. J. Howe, et al., “Structure-Based Design of Novel HIV Protease In- hibitors: Carboxamide-Containing 4-Hydroxycoumarins and 4-Hydroxy-2-pyrones as Potent Nonpeptidic Inhibi- tors,” Journal of Medicinal Chemistry, Vol. 38, No. 18, 1995, pp. 3624-3630. doi:10.1021/jm00018a023 [14] D. Yu, M. Suzuki, L. Xie, S. L. Morris-Natschke and K. H. Lee, “Recent Progress in the Development of Coumarin Derivatives as Potent Anti-HIV Agents,” Medicinal Research Reviews, Vol. 23, No. 3, 2003, pp. 322-328. doi:10.1002/med.10034 [15] J. W. Erickson and S. K. Burt, “Structural Mechanisms of HIV Drug Resistance,” Annual Review of Pharmacology and Toxicology, Vol. 36, 1996, pp. 545-571. doi:10.1146/annurev.pa.36.040196.002553 [16] I. Kostova, S. Raleva, P. Genova and R. Argirova, “Structural Features of Antitumor Titanium Agents and Related Compounds,” Bioinorganic Chemistry and Appli- cations, Vol. 3, No. 3-4, 2005, pp. 317-329. doi:10.1155/BCA.2005.317 [17] A. J. Vlietinck, T. de Bruyne, S. Apers and L. A. Pieters, “Plant-Derived Leading Compounds for Chemotherapy of Human Immunodeficiency Virus (HIV) Infection”, Medicinal Chemistry Research, Vol. 64, 1998, pp. 97- 102. [18] J. B. Harborne and T. J. Mabry, “Title of This Paper,” Chem Abstr, Vol. 119, No. *, pp. 180774-******. [19] K. Kostka, “Chromone Derivatives. VI. Reaction of Phenylhydrazine with Chromone and x-Formyl-o-Hydro- Xyacetophenone,” Polish Journal of Chemistry, Vol. 47, 1973, pp. 305-313 [20] E. O. Nuzum, P. J. Rosenthal and J. H. Mckerrow, “In Vitro Antimalarial Activity of Chalcones and Their Derivatives,” Journal of Medicinal Chemistry, Vol. 38, No. 26, 1995, pp. 5031-5037. doi:10.1021/jm00026a010 [21] A. Nayak and A. S. Mittra “4,4-Bis-5-Pyrazolones and Their 4,4-Unsaturated Products for Possible Use as Fungicides,” Journal of the Indian Chemical Society, Vol. 57, 1980, pp. 643-649 [22] O. Nerya, R. Musa, S. Khatib, S. Tamir, Vaya, “Chalcones as Potent Tyrosinase Inhibitors: The Effect of Hydroxyl Positions and Numbers,” Phytochemistry, Vol. 65, No. 10, 2004, pp. 1389-1395. doi:10.1016/j.phytochem.2004.04.016 [23] Z. N. Siddiqui, G. Khuwaja and M. Asad, “Synthesis of Novel Heterocycles from 3-(3-Alkyl-5-Mercapto-1,2,4- Triazolyliminomethyl) Chromones,” Heterocyclic Commun, Vol. 12, No. 6, 2006, pp. 443-448 [24] L. Santana, E. Uriarte, L. via Dalla and O. Gia, “A New Benzoangelicin with Strong Photobiological Activity,” Bioorganic & Medicinal Chemistry Letters, Vol. 10, No. 6, 2000, pp. 135-137. doi:10.1016/S0960-894X(99)00640-X [25] R. H. Wiley and C. H. Jarboe, “Synthesis of Pyrazolines by the Reactions of α,β-enones with Diazomethane and Hydrazines,” Chemistry of Heterocyclic Compounds, Vol. 33, No. 6, 1997, pp. 647-659, doi:10.1007/BF02291794 [26] K. C. Fylaktakidou, D. J. Hadjipavlou-Litina, K. E. Litinas and D. N. Nicolaides, “Natural and Syntheticcoumarin Derivatives with Anti-Inflammatory and Antioxidant Activity,” Current Pharmaceutical Design, Vol. 10, No. 6, 2004, pp. 3813-3833 [27] S. Kirkiachiarian, R. Bakhchinian, H. Chidiak, M. Mazmanian and C. Planche, “Two New Flavonoids and Other Constituents in Licorice Root; Their Relative Astringency and Radical Scavenging Effects,” Annales Pharmaceutiques Fran?aises, Vol. 57, No. 5, 1999, pp. 251-259. [28] J. R. Soares, T. C. P. Dins, A. P. Cunha and L. M. Ameida, “Antioxidant Activity of Some Extracts of Thymus Zygis,” Free Radical Research, Vol. 26, No. 5, 1997, pp. 469-476. doi:10.3109/10715769709084484