Abstract
In the present study, some novel fluorine-containing heterocycles incorporating benzofuran with dihydropyrazoles and dihydroisoxazoles have been synthesized and evaluated for their in vitro antibacterial and antifungal activities. 2-Acetylbenzofuran on treatment with fluorinated aldehydes afforded corresponding fluorine-containing 1-benzofuran-2-yl-3-phenyl-prop-2-en-1-ones (chalcones 5a–g). The cyclocondensation of chalcones (5a–g) with hydrazine hydrate under basic conditions resulted in formation of corresponding novel fluorine-containing 3-benzofuran-2yl-5-phenyl-4,5-dihydro-1H-pyrazoles (6a–g). Similar reaction with hydroxylamine hydrochloride yielded 3-benzofuran-2yl-5-phenyl-4,5-dihydro-isoxazoles (7a–g). All the synthesized compounds have been characterized on the basis of analytical and spectral data, and were screened for their antibacterial and antifungal activities. Some of the synthesized compounds showed good antibacterial and antifungal activities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdel-Wahab BF, Abdel-Aziz HA, Ahmed EM (2008) Convenient synthesis and antimicrobial activity of new 3-substituted 5-(benzofuran-2-yl)-pyrazole derivatives. Arch Pharm Chem Life Sci 341:734–739
Bansal E, Srivastava VK, Kumar A (2001) Synthesis and antiinflammatory activity of 1-acetyl-5-substituted aryl-3-(b-aminonaphthyl)-2-pyrazolines and b-(substituted aminoethyl) amidonaphthalenes. Eur J Med Chem 36:81–92
Basawaraj R, Yadav B, Sangapure SS (2001) Synthesis of some 1H-pyrazolines bearing benzofuran as biologically active agents. Indian J Heterocycl Chem 11:31–34
Caramella P, Gruenanger P (1984) In: Padwa A (Ed) 1,3-Dipolar cycloaddition chemistry, vol 1, Wiley, New York, p 337
Carson CF, Hammer KA, Riley TV (1995) Broth micro-dilution method for determining the susceptibility of Escherichia coli and Staphylococcus aureusto the essencial oil of Melaleuca alternifolia (tea tree oil). Microbios 82:181–185
Cho JU, Kim CJ, Lee HB, Lim CH (2004) Patent Korea KR 2004064795 (CA: 145, 182279)
Corey EJ (1973) In: ApSimon J (ed) The Total Synthesis of Natural Products vol. 1. Wiley, New York, p 81
Dai JR, Hallock YF, Cardellina JH, Boyd M (1998) HIV-inhibitory and cytotoxic oligostillbenes from the leaves of Hopea malibato. J Nat Prod 61:351–353
Dawood KM, Abdel-Gawad H, Rageb EA, Ellithey M, Mohamed HA (2006) Synthesis, anticonvulsant, and anti-inflammatory evaluation of some new benzotriazole and benzofuran-based heterocycles. Bioorg Med Chem 14:3672–3680
Diyasena MNC, Sotheeswaran S, Surendrakumar S, Balasubramanian S, Bokel M, Karus WJ (1985) Balanocarpol, a new polyphenol from Balanocarpus zeylanicus (trimen) and Hopea jucunda (Thw.) (Dipterocarpaceae). J Chem Soc Perkin Trans 1:1807–1809
Druzgala P, Milner PG (2002) Novel enantiomeric compounds for treatment of cardiac arrhythmias and methods of use. US Patent Appl Publ 2002193428 (CA: 138, 39179)
Du X, Guo C, Hansell E, Doyle PS, Caffrey CR, Holler TP, McKerrow JH, Cohen FE (2002) Synthesis and structure–activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain. J Med Chem 45:2695–2707
Engler TA, LaTessa KO, Iyengar R, Chai W, Agrios K (1996) Stereoselective syntheses of substituted pterocarpans with anti-HIV activity, and 5-aza-/5-thia-pterocarpan and 2-aryl-2,3-dihydrobenzofuran analogues. Bioorg Med Chem 4:1755–1769
Fuganti C, Serra S (1998) A new approach to 2-aryl-7-alkoxy-benzofurans: synthesis of ailanthoidol, a natural neolignan. Tetrahedron Lett 39:5609–5610
Gokhan N, Yeilada A, Uçar G, Erol K, Bilgin AA (2003) 1-N-Substituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines. synthesis and evaluation as mao inhibitors. Arch Pharm 336:362–371
Havrylyuk D, Zimenkovsky B, Vasylenko O, Zaprutko L, Gzella A, Lesyk R (2009) Synthesis of novel thiazolone based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur J Med Chem 44:1396–1404
Huisgen R (1963) 1,3-Dipolar cycloadditions. Angew Chem Int Ed 2:565–598
Mana F, Chimenti F, Bolasco A, Cenicola ML, Parrillo MDC, Rossi F, Marmo E (1992) Anti-inflammatory, analgesic and antipyretic N-acetyl-2-pyrazolines and dihydrothieno coumarines. Eur J Med Chem 27:633–639
Nasr MNA, Said SA (2003) Novel 3,3a,4,5,6,7-hexahydroindazole and arylthiazolyl pyrazoline derivatives as anti-inflammatory agent. Arch Pharm 336:551–559
Paizs C, Tosa M, Majdik C, Moldovan P, Novak L, Kolonits P, Marcovivi A, Irimie F, Poppe L (2003) Optically active 1-(benzofuran-2-il)ethanols and ethane-1,2-diols by enantiotopic selective bioreductions. Tetrahedron Asym 14:1495–1501
Palaska E, Aytemir M, Uzbay IT, Erol E (2001) Synthesis and antidepressant activities of some 3,5-diphenyl-2-pyrazolines. Eur J Med Chem 36:539–543
Purser S, Moore PR, Swallow S, Gouverneur V (2008) Fluorine in medicinal chemistry. Chem Soc Rev 37:320–330
Rida SM, EI-Hawash SAM, Fahmy HTY, Hazzaa AA, EI-Meligy MMM (2006) Synthesis of novel benzofuran and related benzimidazole derivatives for evaluation of in vitro anti-HIV-1, anticancer and antimicrobial activities. Arch Pharm Res 29:826–833
Riesselman MH, Hazen KC, Cutler JE (2000) Determination of antifungal MICs by a rapid susceptibility assay. J Clin Microbiol 38:333–340
Rowley M, Hallett DJ, Goodacre S, Moyes C, Crawforth J, Sparey TJ, Patel S, Marwood R, Patel S, Thomas S, Hitzel L, Connor DO, Szeto N, Castro JL, Hutson PH, Macleod AM (2001) 3-(4-Fluoropiperidin-3-yl)-2-phenylindoles as high affinity, selective, and orally bioavailable h5-HT2Areceptor antagonists. J Med Chem 44:1603–1614
Shaharyar M, Abdullah MM, Bakht MA, Majeed J (2010) Pyrazoline bearing benzimidazoles: search for anticancer agent. Eur J Med Chem 45:114–119
Singh DV, Mishra AR, Mishra RM, Pandey AK, Singh CR, Dwivedi AK (2005) Synthesis and fungicidal activity of benzofuran incorporated substituted pyrimidines. Indian J Heterocycl Chem 14:319–322
Smart BE (2001) Fluorine substutuent effects (on bioactivity). J Fluorine Chem 109:3–11
Tarpay MM, Welch DF, Marks MI (1980) Antimicrobial susceptibility testing of Streptococcus pneumoniae by micro-broth dilution. Antimicrob Agents Chemother 18:579–581
Teresa MVD, Mello PE (2005) Review article: recent advances on the synthesis and reactivity of isaxazoles. Current Org Chem 9:925–958
Turan-Zitouni G, Chevallet P, Kiliç FS, Erol K (2000) Synthesis of some thiazolyl-pyrazoline derivatives and preliminary investigation of their hypotensive activity. Eur J Med Chem 35:635–641
Ujjinamatada RK, Appala RS, Agasimundin YS (2006) Synthesis and antimicrobial activity of new benzofuranyl-1,3-benzoxazines and 1,3-benzoxazin-2-ones. J Heterocycl Chem 43:437–441
Wachi S, Takagi K, Menichi G, Hubert-Habart M (1978) Research on potential antitumor agents. Methods for preparing hydropyrimidines from coumarins. Bull Soc Chim Fr 5–6:230–233
Acknowledgments
The authors thank to Department of Science & Technology (DST), New Delhi and University Grants Commission (UGC) for providing financial support. We gratefully acknowledge USIC, University of Delhi for providing analytical support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chundawat, T.S., Sharma, N. & Bhagat, S. Synthesis and in vitro antimicrobial evaluation of novel fluorine-containing 3-benzofuran-2-yl-5-phenyl-4,5-dihydro-1H-pyrazoles and 3-benzofuran-2-yl-5-phenyl-4,5-dihydro-isoxazoles. Med Chem Res 23, 1350–1359 (2014). https://doi.org/10.1007/s00044-013-0735-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-013-0735-9