INTRODUCTION:

Chalcones (trans-1,3-diphenyl-2-propen-1-ones) are the biogenetic precursors of all known flavonoids and are abundant in edible plants.1 Chemically, they consist of open-chain flavonoids in which the two aromatic rings are joined by a three carbon a,ß- unsaturated carbonyl system (Figure 1). Chalcones present a broad spectrum of biological activities,^1-2 such as anticancer, anti-inflammatory, antimalarial, antifungal,^3-4 antilipidemic, and antiviral activities.⁵ For example, xanthoangelol has been reported to induce apoptosis and to inhibit tumor promotion and metastasis in several cancer cell lines.^6-7 Broussochalcone A,⁸dimethylaminochalcones, ⁹ and cardamonin,¹⁰ possess anti-inflammatory activity,¹¹ Licochalcone A, a substance found in the roots of the Chinese liquorice, showed antimalarial activity,¹² 4’,4-Dichlorochalcone exhibits antilipidemic activity,¹³ (Figure 2).

Figure 1. General chemical structure of synthesized trans-chalcones.

There are other chalcones with very interesting biological activity such as butein,¹⁴ and soliquiritigen in.¹⁰ These chalcones, like trans-resveratrol,¹⁵ remarkably activate sirtuin,¹⁶ enzymatic activity, mimic the beneficial effects of caloric restriction (CR), retard the aging process, and increase longevity in the budding yeast Saccharomyces cereVisiae.

Figure 2. Structures of known trans-chalcones with biological activities.

MATERIALS AND METHODS:

Reaction scheme:

Reagent : 20% NaOH, Ethanol, MW irradiation

Scheme-1: (4-methylphenyl)-3-(3- phenoxyphenyl)prop-2-en-1-one (3a-e)

Laboratory chemicals were supplied by Spectrochem India Ltd. and Fisher Scientific Ltd. All Melting points were determined using the open tube capillary method and were uncorrected. Purity of the compounds was determined by thin layer chromatography (TLC) plates (silica gel G) in the solvent system ethyl acetate: toluene (1:3) the spots were observed by exposure to iodine vapours or by UV light. The IR spectra were obtained on a Perkin-Elmer spectrum 65 FT-IR spectrometer (KBr pellets) in range 4000-400 cm^-1.The ¹H and ¹³C-NMR spectra were recorded on a Bruker Avance II 400 spectrometer using TMS as the internal standard in CDCl₃. Elemental analysis of the newly synthesized compounds were carried out on Carlo Erba 1108 analyzer. The reaction was carried out in unmodified microwave oven (Kenstar, output energy 1200W, frequency 2450 MHz model No.M69706)

Procedure for the synthesis (1-(4-methylphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one 3a-e

a. Solution phase conventional method:

A solution of m-phenoxy benzaldehyde (0.01 mole) and substituted aromatic acetophenones (0.01 mole) in ethanol (20 mL) taken in a Round bottom flask (100 mL), a 20% solution of sodium hydroxide slowly added under agitation and stirrer overnight. then reaction mixture was cooled, reaction mass poured on crushed ice and neutralized by dilute HCl, product was filtered washed with water, dry and recrystallized by ethanol. Yield :65-75%

b. General process for Microwave assisted synthesis of chalcones:

To a solution of m-phenoxy benzaldehyde (0.01 mole) and substituted aromatic acetophenones (0.01 mole) in ethanol (20 mL) taken in a conical flask (100 mL), a 20% solution of sodium hydroxide slowly addeded under agitation and the reaction mixture was heated inside a microwave oven for 30 sec to 180 sec. (at 210 Watts, i.e. 30% microwave power). The reactions were monitored through TLC using solvent system (a) ethyl acetate : n-hexane (1:3),) When the reaction was found to be complete, then reaction mixture was cooled, reaction mass poured on crushed ice and neutralized by dilute HCl, product was filtered washed with water, dry and recrystallized by ethanol. Yield :80-92(Scheme-1)

The characterization data of synthesized compound 3a-e are given below.

Compound (3a): light yellow needle crystal, m.p.60°C (Found: C, 83.52; H 5.42; F, 6.01; O, 5.06.cald. For C₂₂H₁₇FO (318.36): C, 83.52; H, 5.42; F, 6.01; O, 5.06 %); IR vmax (KBr, cm^-1): 1663 (conjugated C=O), 1590,1486,(C=C/Ar), 1156, 979 (CH=CH,Trans),838, 689 (substituted phenyl), 1208 (phenyl C-O);MS: m/z (%) 318, (M+1), 301(31), 249(24); (¹H NMR, δH,CDCl_3,ppm) ; 6.9-8,(m, 11H, Ar-H); 7.5-7.9(-CH=CH-)

Compound (3b): light yellow needle crystal, m.p.70°C (Found: C, 79.98; H, 5.49; O, 4.53. Calcd. For C₂₂H₁₈O₃ (330.37); C, 79.98; H, 5.49; O, 14.53%) IR ν_max (KBr cm^-1): 3007 (Ar-H), 1655 (conjugation C=O), 1599, 1575 (C=C/Ar), (987, 838 CH=CH, Trans), 1261 (C-O/Ar) ; MS: m/z (%) 474 (48); 453 (46) MS: m/z (%) 330 (33); 223 (22) (¹H NMR, δH,CDCl_3,ppm) ;3.9 (s. 3H,OCH₃), 6.9-8,(m, 11H, Ar-H); 7.5-7.9(-CH=CH-)

Compound (3c): yellow solid, m.p.90°C (Found: C, 53.2; H, 2.98; Br, 33.7; O, 10.12 Calcd. For C₂₁H₁₄Br₂O₃(474.14); C, 53.2; H, 2.98; Br, 33.7; O, 10.12%) IR V_max(KBr cm^-1): 3300 (OH), 1660 (conjugation C=O), 1575, 1478 (C=C/Ar), (1128, 979 CH=CH, Trans), 1261 (C-O/Ar) ; 842, 669 (substituted phenyl); MS: m/z (%) 474 (48); 453 (46) (¹H NMR, δH,CDCl_3,ppm) ; 5 (s. 1H,OH), 6.9-8,(m, 11H, Ar-H); 7.5-7.9(-CH=CH-)

Compound (3d): light yellow needle crystal, m.p.140°C (Found C, 81.43; H 6.57; N, 3.65; O, 8.34.cald. For C₂₆H₂₅NO₂ (383.48): C, 81.43; H, 6.57; N,3.65; O, 8.34%); IR ν_max (KBr, cm^-1): 1651 (conjugated C=O), 1579,1490,(C=C/Ar), 1257, 987 (CH=CH,Trans),818, 769 (substituted phenyl); MS: m/z (%) 383, (M+1), 204(20); (¹H NMR, δH,CDCl_3,ppm) ;1.5-3 (m,10H, pipyridine) 6.9-8,(m, 11H, Ar-H); 7.5-7.9(-CH=CH-)

Compound (3e): light yellow needle crystal, m.p.68°C (Found: C, 75.34; H 4.52; Cl, 10.59; O, 9.56.cald. For C₂₁H₁₅ClO₂ (334.79): C, 75.34; H, 4.52; Cl, 10.6; O, 9.5 %); IR ν_max (KBr, cm^-1): 1659(conjugated C=O), 1607,1482,(C=C/Ar), 1232, 979 (CH=CH,Trans),778, 689 (substituted phenyl); MS: m/z (%) 334, (M+1), 319(32); (¹H NMR, δH,CDCl_3,ppm) ; 1.56.9-8,(m, 11H, Ar-H); 7.5-7.9(-CH=CH-)

Compound (3f): light yellow needle crystal, m.p.55°C (Found: C, 84.05; H 5.77; O, 10.08.cald. For C₂₂H₁₈O₂ (314.37): C, 84.05; H, 5.77; O, 10.08 %); IR ν_max (KBr, cm^-1): 1659 (conjugated C=O), 1598,1487,(C=C/Ar), 1251, 977 (CH=CH,Trans),769, 691 (substituted phenyl); MS: m/z (%) 314 (M+1), 301(31); (¹H NMR, δH,CDCl_3,ppm) ; 2.3 (s, 3H, CH₃); 6.9-8,(m, 11H, Ar-H); 7.5-7.9(-CH=CH-)

Biological activities of compound 3a-e:

Antifungal activities of compounds 3a-e found and mould fungi were studied, viz., Candida albicans, Aspergillus fumigatus), Sabouraud dextrose agar was used as basal medium for test fungi. Glass Petri dishes used were sterilized.Sterilized melted medium (~ 45oC) was poured at the rate of 15 ml into each Petri dish (90 mm). After solidification of the medium, small portions of the mycelium of each fungus were spread carefully over the centre of each PDA plate with the help of sterilized needles. Thus, each fungus was transferred to a number of PDA plates, which were then incubated at (25 ± 2) °C and ready for use after five days of incubation.

Prepared discs of samples were placed gently on solidified agar plates, freshly seeded with the test organisms with sterile forceps. A control disc was also placed on the test plates to compare the effect of the test samples and to nullify the effect of solvent respectively. The plates were then kept in a refrigerator at 4°C for 24 h so that the materials had sufficient time to diffuse over a considerable area of the plates. After this, the plates were incubated at 37×5°C for 72 h. Dimethyl Formamide (DMF) wasused as solvent to prepare desired solutions (20 mg/ ml) of the compounds initially and to maintain proper control.

*S.No.*	*Aspergillus fumigatus*	*Candida albicans*
3a	++	++
3b	++	++
3c	++	--
3d	++	--
3e	++	--
Standard	10 mm (No activity)	20 mm

ACKNOWLEDGEMENT:

The authors wish to express their thanks to Dr. Y.S. Jhala, Principal, B.N.P.G. College, Udaipur (Raj.) for providing necessary facilities, SAIF, Chandigarh Punjab University for elemental and spectral data and to the Head, Department of Microbiology, college of science MLSU University, Udaipur of antibacterial activity.

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Received on 29.03.2013 Modified on 12.04.2013

Asian J. Research Chem. 6(5): May 2013; Page 461-463