Synthesis and Anti-Inflammatory Activity of some New Chalcones from 3' - Methyl- 4' Hydroxyacetophenone

Transcription

1 Synthesis and Anti-Inflammatory Activity of some New Chalcones from 3' - Methyl- 4' Hydroxyacetophenone 02 N. Srinath *, Y. Rajendra Prasasd, K. Mukkanti 2, C. Kistayya and B. Bhaskar Rao Department of Pharmacy, Acharya Nagarjuna University, Guntur 52250, A.P., India University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam , A.P., India 2 Centre for Pharmaceutical Sciences, J N T University, Hyderabad *For Correspondence - srinath_n2k@rediffmail.com Abstract A series of some new chalcones were synthesized by Claisen-Schmidt condensation of 3'-methyl-4'-hydroxyacetophenone with various substituted aromatic / heteroaromatic aldehydes in the presence of alkali. The resulting chalcones were characterized by IR, H NMR and Elemental analysis. These chalcones were evaluated for their anti-inflammatory activity and some of them exhibited significant activity when compared with the standard. Key words: Chalcones, Synthesis, Anti-inflammatory activity Introduction Chalcone is a generic term given to compounds bearing the, 3-diphenylprop-2-en--one frame work, which can be functionalized in the propane chain by the presence of olefinic, keto and / or hydroxyl groups (Fig. (. Chalcones have been reported to exhibit a wide variety of pharmacological activities including antioncogenic (2, antiulcerative (3, analgesic and anti-inflammatory (4, antiviral (5, antimalarial (6 and antibacterial (7 activities. The presence of a reactive á, â unsaturated keto function is partly responsible for their activities. Chalcones are readily synthesized by the base catalyzed Claisen Schmidt condensation of an aldehyde and an appropriate ketone in a polar solvent like ethanol and yields may be variable (8,9 ranging from 5 to 80%. In the present communication, we report the reaction of 3'-methyl-4'-hydroxyacetophenone with different aromatic / heteroaromatic aldehydes to form chalcones (B B 5. The structures of all the synthesized compounds were assigned on the basis of IR, H NMR spectral data and Elemental analysis. These compounds were also screened for their anti-inflammatory activity. Fig. Experimental Melting points were determined in open capillary tubes and are uncorrected. The IR spectra were recorded in KBr on Perkin Elmer 337 Infrared Spectrophotometer. The H NMR were recorded in CDCl 3 on Bruker AMX 400MHz NMR Spectrophotometer using TMS as an internal standard. The Elemental analysis was performed on Perkin Elmer model 2400 series II apparatus. The purity of the compounds was checked by TLC using Silica gel-g (Merck. Column chromatography was performed on Silica gel (Merck, mesh. Synthesis and Anti-Inflammatory

2 022 General Procedure for the Preparation of Chalcones : A mixture of 3'-methyl-4'- hydroxyacetophenone (0.005 mol and various substituted aromatic / heteroaromatic aldehydes (0.005 mol was stirred in ethanol (30 ml manually at room temperature for 0 minutes, kept and then an aqueous solution of 50% potassium hydroxide (7.5 ml was added to it. The mixture was kept overnight at room temperature and then it was poured into crushed ice and acidified with dilute hydrochloric acid. The chalcone derivatives precipitated out as solid. Then it was filtered and crystallized from ethanol (Scheme. This procedure remained same with all types of aldehydes. 3'-methyl-4'-hydroxyacetophenone Aldehyde Chalcone Scheme Where Ar = Physical Characterization Data of Chalcones -(3' Methyl -4'-hydroxyphenyl-3-(2' - pyridinyl-2-propen--one (B Yield: 85%; m.p C IR (KBr, cm - : 3628 (O-H, 65 (C=O, 58 (C=N, Physical Characterization Data of Chalcones o N H N H N Br Srinath et al

3 (C=C Quadrant of Ar, 464 (CH=CH, äppm: 7.96 (H,d,J=7Hz, =CH-Ar, 7.83 (H,s,J=7Hz, -CO-CH=,7.92 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,8.50 (H,d, J=7.2Hz,C-3' -H, 7.8 (H,m,J=7.3Hz,C-4' -H,7.7 (H,m,C-5' - H,7.78 (H,d,J=8Hz,C-6' -H Anal.Calcd.for C 5 H 3 N0 2 : C, 75.30; H, 5.480; N, Found: C, 75.23; H, 5.434; N, (3' Methyl -4'-hydroxyphenyl-3-(3' - pyridinyl-2-propen--one (B 2 Yield: 82%; m.p C IR (KBr, cm - : 3627 (O-H, 65 (C=O, 582 (C=N, 505 (C=C Quadrant of Ar, 465 (CH=CH, äppm: 7.7 (H,d,J=7Hz, =CH-Ar, 7.32 (H,d,J=7Hz, -CO-CH=, 7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H,7.80 (H,d,J=8.6Hz,C-6'- H,8.86 (H,s,C-2' -H,8.65 (H,d,J=7.3Hz,C-4' - H,7.38 (H,m,J=8Hz,C-5' -H,7.96 (H,d,J=8Hz, C -6' -H Anal.Calcd.forC 5 H 3 N0 2 : C, ; H, 5.483; N, Found: C, 75.83; H, 5.463; N, (3' Methyl -4'-hydroxyphenyl-3-(4' - pyridinyl-2-propen--one (B 3 Yield: 75%; m.p C IR (KBr, cm - : 3625 (O-H, 650 (C=O, 583 (C=N, 503 (C=C Quadrant of Ar, 466 (CH=CH, äppm: 7.60 (H,d,J=7Hz, =CH-Ar,7.74 (H,d,J=7Hz, CO-CH=,7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,7.32 (H,d,J=7.2Hz,C-2' -H, 8.52 (H,d,J=7.2Hz,C-3' -H,8.65 (H,d,J=7.2Hz,C-5' -H, 7.32 (H,d,J=7.2Hz,c-6' -H Anal.Calcd.forC 5 H 3 N0 2 : C, ; H, 5.483; NFound: C, ; H, 5.458; N, (3' Methyl -4'-hydroxyphenyl-3-(2' - furyl-2-propen--one (B 4 Yield: 63%; m.p C IR (KBr, cm - : 3626 (O-H, 652 (C=O, 505 (C=C Quadrant of Ar, 463 (CH=CH, 200 (C-O, äppm: 7.59 (H,d,J=7Hz, =CH-Ar,7.46 (H,d,J=7Hz, -CO-CH=,7.85 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.8 (H,d,J=8.6Hz,C-6'-H,6.66 (H,d, J=7.2Hz,C-3' -H, 6.43 (H,d,J=7.2Hz,C-4' -H,7.45 (H,s,C-5' -H Anal.Calcd. for C 4 H : C, ; H, Found: C, ; H, (3' Methyl -4'-hydroxyphenyl-3-(2' - pyrrolyl-2-propen--one (B 5 Yield: 64%; m.p C IR (KBr, cm - : 3624 (O-H, 653 (C=O, 580 (C=N, 504 (C=C Quadrant of Ar, 465 (CH=CH H-NMR (CDCl 3, äppm: 7.7 (H,d,J=7Hz,=CH-Ar,6.94 (H,d,J=7Hz,-CO- CH=,7.8 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.79 (H,d,J=8.6Hz,C-6'-H,6.25 (H,d,J=7.2Hz,C-3' -H 5.98 (H,m,J=7.2Hz,C-4' -H,6.99 (H,d,J=6.8Hz,C-5' -H Anal.Calcd.forC 4 H 3 NO 2 : C, ; H, 5.772; N, 6.6. Found: C, 74.02; H, 5.742; N, (3' Methyl -4'-hydroxyphenyl-3-(2' - thienyl-2-propen--one (B 6 Yield: 73%; m.p C IR (KBr, cm - : 3625 (O-H, 650 (C=O, 505 (C=C Quadrant of Ar, Synthesis and Anti-Inflammatory

4 (CH=CH, 650 (C-S, äppm: 7.93 (H,d,J=7Hz,=CH-Ar,7.8 (H,d,J=7Hz,-CO- CH=,7.88 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.78 (H,d,J=8.6Hz,C-6'-H,7.55 (H,d,J=7.2Hz,C-3' -H 7.6 (H,m,J=7.2Hz,C-4' -H,7.6 (H,d,J=6.8Hz,C-5' -H Anal.Calcd. for C 4 H 2 S0 2 : C, ; H, Found: C, 68.92; H, (3' Methyl -4'-hydroxyphenyl-3-(2' - indolyl-2-propen--one (B 7 Yield: 85%; m.p C IR (KBr, cm - : 3623 (O-H, 655 (C=O, 585 (C=N, 506 (C=C Quadrant of Ar, 467 (CH=CH, äppm: 7.83 (H,d,J=7Hz,=CH-Ar,7.35 (H,d,J=7Hz,-CO- CH=,7.97 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.83 (H,d,J=8.6Hz,C-6'-H,7.92 (H,d,J=7.2Hz,C-2' -H, 7.93 (H,d,J=7.8Hz,C-4' -H,7.9 (H,d,J=7.8Hz,C-5' -H 7.3 (H,d,J=7.9Hz,C-6' -H,7.45 (H,d,J=7.9Hz, C-7' -H Anal.Calcd.forC 8 H 5 NO 2 : C, ; H, 5.453; N, Found: C, 77.72; H, 5.52; N, (3' Methyl -4'-hydroxyphenyl-3-(2' - quinolinyl-2-propen--one (B 8 Yield: 84%; m.p C IR (KBr, cm - : 3628 (O-H, 654 (C=O, 582 (C=N, 504 (C=C Quadrant of Ar, 464 (CH=CH, äppm: 7.82 (H,d,J=7Hz,=CH-Ar,7.75 (H,d,J=7Hz,-CO- CH=,7.7 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.62 (H,d,J=8.6Hz,C-6'-H,7.64 (H,d,J=8.5Hz,C-3' -H 7.86 (H,d,J=8.5Hz,C-4' -H,7.78 (H,d,J=7.9Hz,C-5' -H 7.69 (H,t,J=7.9Hz,C-6' -H,7.63 (H,t,J=7.9Hz, C-7' -H, 7.68 (H,d,J=7.9Hz,C-8' -H Anal.Calcd.forC 9 H 5 NO 2 : C, ; H, 5.8; N, Found: C, ; H, 5.223; N, (3' Methyl -4'-hydroxyphenyl-3-(9' - anthracenyl-2-propen--one (B 9 Yield: 86%; m.p C IR (KBr, cm - : 3627 (O-H, 655 (C=O, 507 (C=C Quadrant of Ar, 463(CH=CH, äppm: 8.9 (H,d,J=7Hz,=CH-Ar,7.78 (H,d,J=7Hz,-CO- CH=,7.99 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.84 (H,d,J=8.6Hz,C-6'-H,8.40 (H,d,J=8.2Hz,C-' -H, 7.02 (H,m,J=8.2Hz,C-2' -H,7.30 (H,m,J=8.Hz,C-3' -H 7.99 (H,d,J=8.Hz,C-4' -H,7.99 (H,d,J=8.Hz,C-5' -H 7.30 (H,m,J=8.Hz, C-6' -H,7.02 (H,m,J=8.2Hz,C-7' -H 7.82 (H,d,J=8.2Hz,C-8' -H,7.80 (H,s, C-0' - H Anal.Calcd. for C 24 H 8 O 2 : C, 85.82; H, Found: C, 85.22; H, (3' Methyl -4'-hydroxyphenyl-3-(4' - fluorophenyl-2-propen--one (B 0 Yield: 78%; m.p C IR (KBr, cm - : 3625 (O-H, 656 (C=O, 506 (C=C Quadrant of Ar, 46 (CH=CH, 20 (C-F H-NMR (CDCl 3, äppm: 7.83 (H,d,J=7Hz,=CH-Ar,7.26 (H,d,J=7Hz,-CO- CH=,7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'- Srinath et al

5 025,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,7.58 (H,d,J=8.6Hz,C-2' -H 6.95 (H,d,J=8.8Hz,C-3' -H,6.96 (H,d,J=8.8Hz,C-5' -H 7.58 (H,d,J=8.6Hz,C-6' -H Anal.Calcd. for C 6 H 3 FO 2 : C, 75.00; H, Found: C, ; H, (3' Methyl -4'-hydroxyphenyl-3-(4' - chlorophenyl-2-propen--one (B Yield: 75%; m.p C IR (KBr, cm - : 3628 (O-H, 650 (C=O, 506 (C=C Quadrant of Ar, 462 (CH=CH, 855 (C-Cl, äppm: 7.76 (H,d,J=7Hz,=CH-Ar,7.47 (H,d,J=7Hz,-CO- CH=,7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,7.55 (H,d,J=8.5Hz,C-2' -H 7.57 (H,d,J=8.5Hz,C-3' -H,7.53 (H,d,J=8.5Hz,C-5' -H 7.55 (H,d,J=8.5Hz,C-6' -H Anal.Calcd. for C 6 H 3 ClO 2 : C, ; H, Found: C, 70.03; H, (3' Methyl -4'-hydroxyphenyl-3-(4' - bromophenyl-2-propen--one (B 2 Yield: 74%; m.p C IR (KBr, cm - : 3624 (O-H, 652 (C=O, 507 (C=C Quadrant of Ar, 464 (CH=CH, 020 (C-Br, äppm: 7.82 (H,d,J=7Hz,=CH-Ar,7.29 (H,d,J=7Hz,-CO- CH=,7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,7.45 (H,d,J=8.6Hz,C-2' -H 7.59 (H,d,J=8.5Hz,C-3' -H,7.56 (H,d,J=8.5Hz,C-5' -H 7.45 (H,d,J=8.6Hz,C-6' -H Anal.Calcd. for C 6 H 3 BrO 2 : C, 60.59; H, Found: C, 60.48; H, (3' Methyl -4'-hydroxyphenyl-3-(4' - methylphenyl-2-propen--one (B 3 Yield: 85%; m.p C IR (KBr, cm - : 3629 (O-H, 653 (C=O, 506 (C=C Quadrant of Ar, 463(CH=CH, äppm: 7.74 (H,d,J=7Hz,=CH-Ar,7.38 (H,d,J=7Hz,-CO- CH=,7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,7.47 (H,d,J=8.Hz,C-2' -H 6.97 (H,d,J=8.Hz,C-3' -H,2.40 (3H,s,C-4' (H,d,J=8.Hz,C-5' -H,7.47 (H,d,J=8.Hz, C-6' -H Anal.Calcd. for C 7 H : C, ; H, Found: C, ; H, (3' Methyl-4'-hydroxyphenyl-3-(4' - methoxyphenyl-2-propen--one(b 4 Yield: 83%; m.p C IR (KBr, cm - : 3627 (O-H, 652 (C=O, 503 (C=C Quadrant of Ar, 46 (CH=CH, 70 (-O-, äppm: 7.80 (H,d,J=7Hz,=CH-Ar,7.37 (H,d,J=7Hz,-CO- CH=,7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,7.56 (H,d,J=8.5Hz,C-2' -H 6.92 (H,d,J=8.5Hz,C-3' -H,3.87 (3H,s,C-4' - O 6.92 (H,d,J=8.5Hz,C-5' -H,7.56 (H,d,J=8.5Hz, C-6' -H Anal.Calcd. for C 7 H : C, 76.02; H, Found: C, 76.00; H, (3' Methyl -4'-hydroxyphenyl-3- (3',4',5' - trimethoxyphenyl-2-propen-- Synthesis and Anti-Inflammatory

6 026 one (B 5 Yield: 80%; m.p C IR (KBr, cm - : 3625 (O-H, 654 (C=O, 505 (C=C Quadrant of Ar, 465 (CH=CH, 75 (-O-, äppm: 7.70 (H,d,J=7Hz,=CH-Ar,7.50 (H,d,J=7Hz,-CO- CH=,7.89 (H,s,C-2'-H,2.30 (3H,s,C-3'-,6.93 (H,d,J=8.6Hz,C-5'-H 7.80 (H,d,J=8.6Hz,C-6'-H,6.80 (H,s,C-2' - H,3.85 (9H,s, 3 x -O 6.80 (H,s,C-6' -H Anal. Calcd. for C 9 H 20 O 5 : C, ; H, Found: C, 69.43; H, 6.8. Anti-Inflammatory activity The anti-inflammatory activity of the synthesized chalcones was evaluated by using carrageenan-induced rat paw oedema method (0,. Albino rats of either sex (50-200g were used in the study. The animals were housed under standard environmental conditions (temperature of 22 ± 0 C with an alternating 2 hour light-dark cycle and relative humidity of 60±5%, fed with standard diet and water ad libitum. Rats were divided into seventeen groups of six animals in each group. Inflammation was induced by injecting 0.05 ml of % carrageenan (Sigma subcutaneously into the sub-plantar region of the right hind paw and 0.05ml saline was injected into the sub-plantar region of the left hind paw for all groups. One hour prior to carrageenan injection, the groups III XVII treated with compounds (B B 5 (0 mg/kg. % Sodium CMC gel (ml/kg was given to group I used as carrageenan treated control and the standard drug aceclofenac (2 mg/kg was administered to group II. All the doses were administered orally. Anti-inflammatory activity was evaluated by measuring carrageenan induced paw oedema. The thickness of the both paws of each rat, lower and upper surface was measured using Zeitlin s constant load level method consisting of a graduated micrometer combined with a constant loaded level system to magnify the small changes in paw thickness during the course of the experiment. The percent increase of paw oedema thickness was determined at 0, 0.5,, 2, 3, 4 and 6 hours after induction of inflammation. The percent increase at each time interval was determined by using the formula: Y t - Y o / Y o x 00 Y t = paw thickness at time t hours (after injection Y o = paw thickness at time 0 hours (before injection The percent inhibition of paw oedema thickness was calculated by using the formula: Percentage inhibition = x 00 -y = 00 y 2 Where Y t = average increase in paw thickness in groups tested with chalcones and the standard Y c = average increase in paw thickness in control The results and statistical analysis of anti-inflammatory activity of aceclofenac and the compounds tested are shown in Table. All values are represented as mean ± SEM (n=6. * P<0.0 compared to reference standard Aceclofenac. Student s t-test. Dosage: Aceclofenac: 2 mg/kg Test compounds: 0 mg/kg body weight of rat. Srinath et alsrinath et al

7 027 Table. Anti-Inflammatory activity of Chalcones Compound Ar % inhibition ± SEM at various time intervals 0.5h.0h 2.0h 3.0h 4.0h 6.0h B 2' -pyridinyl 6± 7± 37± 45± 76± 78± B 2 3' -pyridinyl 6± 7± 36± 45± 75± 77± B 3 4' -pyridinyl 6± 7± 35± 46± 74± 78± B 4 2' -furyl 5± 6± 33± 45± 72± 75± B 5 2' -pyrrolyl 3± 5± 52± 64± 93± 97± B 6 2' -thienyl 7± 9± 39± 50± 79± 80± B 7 2' -indolyl 4± 7± 54± 65± 95± 98± B 8 2' -quinolinyl 7± 8± 38± 48± 77± 79± B 9 9' -anthracenyl 0± 2± 45± 56± 85± 90± B 0 4' -fluorophenyl 9± ± 43± 55± 82± 87± B 4' -chlorophenyl 8± ± 42± 53± 8± 85± B 2 4' -bromophenyl 8± 0± 40± 52± 80± 82± B 3 4' -methylphenyl 2± 3± 49± 58± 90± 94± B 4 4' -methoxyphenyl ± 3± 47± 57± 88± 9± B 5 3',4',5' - trimethoxyphenyl 3± 4± 5± 6± 92± 95± Aceclofenac (standard 2± 23± 56± 67± 96± 99± Results and Discussion The anti-inflammatory activity of the some newly synthesized chalcones (B -B 5 has been evaluated by using carrageenan-induced rat paw oedema method. The results of the evaluation have been viewed by taking aceclofenac as the standard drug. The results of anti-inflammatory activity revealed that the compounds B to B 5 exhibited moderate to considerable activity when compared with reference standard aceclofenac, but not at an identical dose level as the standard drug was tested at 2 mg/kg, whereas the chalcones were tested at a dose of 0 mg/kg. From the results it is evident that all the chalcones showed some degree of antiinflammatory activity. However, it is found that the chalcone having indole substituent (B 7 displayed significant anti-inflammatory activity from 3 rd hour onwards and reached the maximum at the 6 th hour and is comparable to that of the standard aceclofenac, but not at an identical dose level. This type of anti-inflammatory activity for this chalcone is understandable since indole derivatives are known to possess significant antiinflammatory activity and a number of drugs belonging to this class are also being used as a NSAIDs. But what is worth noticing is the retention of such activity even in the case of chalcones bearing this moiety. This suggests chalcones can be prepared having other substituted indole moieties in order to enhance the activity further. The next compound in order of potency is the one having a pyrrole substituent (B 5. This was followed by compounds having Synthesis and Anti-Inflammatory

8 028 electron releasing groups as seen in the case of compound B 5, B 3 and B 4. This clearly reveals the importance of electron releasing groups on the aromatic ring in enhancing the antiinflammatory activity and hence attempts can be made to synthesize chalcones having a number of such electron releasing substituents at different positions of the aromatic ring as part of preparing more potent compounds. However, the contributing physicochemical properties for the anti-inflammatory activity of the chalcones need to be established by detailed QSAR studies, which may provide insights into the structural requirements of this class of molecules. Further studies are required to establish the mechanism of anti-inflammatory activity of these compounds, even though literature reports suggest the inhibition of COX-2 enzyme in some cases. Conclusions Chalcones with heterocyclic nucleus such as indole, pyrrole and also the substituents with electron releasing groups such as methoxy, methyl showed better anti-inflammatory activity. Compounds having pharmacophores such as fluoro, chloro, bromo groups have exhibited moderate anti-inflammatory activity. These results suggest that s the chalcone derivatives have excellent scope for further development as commercial anti-inflammatory agents. References. Bohm, B.A. (998 In: Introduction to Flavanoids, Harwood Academic Publishers, Amsterdam. 2. Kumar, S.K., Hager, E., Pettit, C., Gurulingappa, H., Davidson, N.E. and Khan, S.R. (2003 Design, synthesis and evaluation of novel boronicchalcone derivatives as antitumor agents. J.Med.Chem., 46: Mukarami, S., Muramatsu, M., Aihara, H. and Otomo, S. (99 Inhibition of gastric H +, K + -ATPase by the antiulcer agent Sofalcone. Biochem. Pharmacol., 42: Viana, G.S., Bandeira, M. A. and Matos, F. (2003 Analgesic and anti-inflammatory effects of chalcones isolated from Myracrodruon urundeuva. J.Phytomedicine., 0: Onyilagna, J.C., Malhotra, B., Elder, M. and Towers, G.H.N. (997 Synthesis and antimicrobial activity of some chalcone derivatives. Can.J.Plant Pathol., 9: Liu, M., Wilairat, P. and Go, L.M (200 Antimalarial alkoxylated and hydroxylated chalcones: structure-activity relationship analysis. J.Med.Chem., 44: Chen, Z-H., Zheng, C-Ji., Sun, L-P. and Piao, H-R. (200 Synthesis of new chalcone derivatives containing a rhodanine-3- aceticacid moiety with potential antibacterial activity. Eur. J. Med. Chem., 45: Prasad, Y.R., Kumar, P.R., Deepti, Ch.A. and Ramana, M.V. (2007 Synthesis and antimicrobial activity of some chalcones of 3-acetylcoumarin and 2-hydroxy--acetonaphthone. Asian.J.Chem., 9: Prasad, Y.R., Kumar, P.R., Srivani, N. and Rao, A.S. (2006 Synthesis and antimicrobial activity of some new chalcone derivatives. Int.J.Chem.Sci., 44: Turner, R.A. (965 In: Screening Methods in Pharmacology, Demic Press, NewYork, p Winter, C.A., Risley, E.A. and Nuss, G.W. (962 Carrageenan induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Exp. Biol. Med., : 544. Srinadh et al