Synthesis and antibacterial activity of some new 2,3-dimethoxy-3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)chromanones

doi:10.1016/j.ejmech.2008.03.028

European Journal of Medicinal Chemistry

Volume 44, Issue 4, April 2009, Pages 1763-1767

https://doi.org/10.1016/j.ejmech.2008.03.028 Get rights and content

Abstract

Seven new 2,3-dimethoxy-3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)chromanones (5) have been synthesized by the oxidation of 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)chromones (4) with iodobenzene diacetate in methanol. The structures of compounds 5 were established by the combined use of ¹H NMR, IR and mass spectra. All the seven compounds (5) were tested in vitro for their antibacterial activity against Gram-positive bacteria namely, Staphylococcus aureus, Staphylococcus epidermidis and Bacillus pumilus and two Gram-negative bacteria namely, Salmonella typhi and Pseudomonas aeruginosa. Three compounds, 5d, 5f and 5g, have displayed antibacterial activity comparable to the commercial antibiotics, Linezolid, Cefaclor and Cefuroxime axetial.

Graphical abstract

Introduction

Flavonoids are a group of natural products present in a wide variety of plants. They are found in seeds, citrus fruits, olive oil, tea and red wine and are commonly consumed with the human diet [1], [2]. Flavonoids exhibit a broad range of biological activities, including antiviral, antiinflammatory, antioxidant, antiallergic, hepatoprotective, antithrombotic and antitumoral actions [3], [4], [5]. Furthermore, these compounds are used in bacteriology, pharmacology and medicine due to their bactericidal activities [6]. On the other hand, substituted pyrazoles also exhibit a broad spectrum of biological activities such as antidiabetic [7], antibacterial [8], [9], [10], antimicrobial [11], [12], [13], [14] and herbicidal [15], [16]. The use of hypervalent iodine reagents such as iodobenzene diacetate (IBD) [17], [18], [19], [hydroxy(tosyloxy)iodo]benzene (HTIB; Koser's reagent) [20], [21], etc. find interesting applications in heterocyclic compounds especially flavonoids. Among the various such applications, one noteworthy example is the oxidation of flavonols with [hydroxy(tosyloxy)iodo]benzene (HTIB) offering an efficient and convenient synthesis of 2,3-dimethoxy-3-hydroxyflavanones (Eq. (1)) [22].

A literature survey revealed that the title compounds 2,3-dimethoxy-3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)chromanones (5) remain unknown. These observations, coupled with the diverse biological properties associated with pyrazole and flavanone derivatives, prompted us to study the scope of the synthetic route outlined in Eq. (1) on the oxidation of 2-pyrazolyl analogues of flavonol (4). There has been a particular interest in the synthesis of flavonoids with a pyrazole ring at position C-2 to find new and more potent biological activities [23]. We report herein synthesis of 5a–5g by the oxidation of 4a–4g using iodobenzene diacetate (IBD) in methanol with an expectation to find new and more potent antibacterial agents.

Section snippets

Chemistry

The starting material 2-pyrazolyl analogues of flavonol 4 needed for the synthesis of 5 were prepared by the cyclization of pyrazolyl analogues of o-hydroxychalcone 3 with hydrogen peroxide (H₂O₂) in KOH–MeOH from our previous work involving Algar Flynn Oymanda (AFO) reaction [23]. The reaction of 4a was carried out by treatment with 1.1 equiv of IBD in methanol by stirring at room temperature for 15–20 min. Usual work-up of the reaction afforded the pure crystalline product 5a in 78% yield.

Conclusion

We described herein an efficient and convenient synthesis of new compounds 5a–5g, thereby emphasizing the increasing utility of organoiodine(III) mediated methods. The results on the antibacterial activity are also encouraging as out of seven compounds tested, three compounds (5d, 5f and 5g) showed good antibacterial activity as displayed in Table 1, Table 2. A comparison of antibacterial activity of these compounds with that of three commercial antibiotics namely Linezolid, Cefaclor and

Experimental

Melting points were determined in open capillaries with electrical melting point apparatus and are uncorrected. The IR spectra were obtained with a Buck Scientific IR M-500 spectrophotometer. The ¹H NMR spectra were recorded on a Bruker (300 MHz) spectrometer using tetramethylsilane as an internal standard. All the new compounds gave satisfactory analytical results (within 0.4 of the theoretical values). The starting material 2-pyrazolyl analogues of flavanol were available from our previous

Medium

Two solid media, namely Muller–Hinton agar (MHA; beef infusion 300 g/L, casein acid hydrolysate 17.5 g/L, starch 1.5 g/L, agar–agar 17 g/L, and distilled water 1000 ml, adjusted to pH 7.4) and soyabean casein digest agar (SCDA; casein enzymatic hydrolysate 17.0 g/L, papain digest of soyabean 3.0 g/L, NaCl 5.0 g/L, dipotassium phosphate 2.5 g/L, dextrose 2.5 g/L, and distilled water 1000 ml, adjusted to pH 7.3), were used for the biological assays.

Test microorganisms

Three Gram-positive bacteria S. aureus (MTCC 3160), S.

Acknowledgements

We are thankful to CSIR, New Delhi for the award of Senior Research Fellowship to Rajesh Kumar. Thanks are also due to RSIC, Lucknow, India, for providing mass and elemental analyses.

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Short communicationSynthesis and antibacterial activity of some new 2,3-dimethoxy-3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)chromanones

Abstract

Graphical abstract

Introduction

Section snippets

Chemistry

Conclusion

Experimental

Medium

Test microorganisms

Acknowledgements

Phytochemistry

Bioorg. Med. Chem.

Eur. J. Med. Chem.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Tetrahedron

Pharmacol. Rev.

Curr. Med. Chem.

Biochem. Soc. Trans.

Biochem. Soc. Trans.

J. Pharm. Pharmacol.

J. Med. Chem.

Mycopathologia

Short communication
Synthesis and antibacterial activity of some new 2,3-dimethoxy-3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl)chromanones