Abstract
A series of 1,3-diaryl-2-propen-1-ones was synthesized by both the conventional and microwave irradiation methods. It was observed that a microwave-assisted method was a convenient, rapid, and high yielding method for the synthesis of 1,3-diaryl-2-propen-1-ones as compared to the conventional method. In vivo acute toxicity studies and analgesic and anti-inflammatory activities of these compounds were also evaluated. The analgesic activity was evaluated using acetic acid-induced writhing method in mice and aspirin as the standard. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema method and indomethacin as the standard. The quantitative structure–activity relationships (QSAR) studies were carried out by correlating, individually, the analgesic activity and the anti-inflammatory activity of the synthesized compounds with their physicochemical descriptors using multiple linear regression method. The predictability of the QSAR model was estimated using internal and external predictivity methods. Most of the synthesized compounds showed significant analgesic and anti-inflammatory activities. Compounds having high molecular weight and electron donating groups showed good analgesic activity. Compounds possessing high molar volume and electron donating substituents showed good anti-inflammatory activity. The compound, 1-(4′-methoxyphenyl)-3-(3″-methoxy-4″-hydroxyphenyl)-2-propen-1-one, showed higher analgesic activity than the standard, aspirin, as well as higher anti-inflammatory activity than indomethacin.
Similar content being viewed by others
References
Ahluwalia VK, Nayal L, Kaila N, Bala S, Tahim AK (1987) Synthesis and antimicrobial activity of substituted 3,4-dihydro-2H-1-benzopyrans. Indian J Chem 26B:384–386
Chen M, Christensen SB, Zhai L, Rasmussen MH, Kharazmi A (1997) The novel oxygenated chalcone, 2,4-dimethoxy-4′-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo. J Infect Dis 176:1327–1333
El-Sabbagh OI, Ibrahim SM, Baraka MM, Kothayer H (2010) Synthesis of new 2,3-dihydroquinazolin-4(1H)-one derivatives for analgesic and anti-inflammatory evaluation. Arch Pharm 343:274–281
Gaede BJ, McDermott LL (1993) Novel perfluoroalkyl-substituted pyrazoles. J Heterocycl Chem 30:49–54
Hsin-kaw H, Tai-Hua L, Wang J, Jey-Jeng W, Chun-Nan L (1998) Synthesis and anti-inflammatory effects of chalcones and related compounds. Pharm Res 15:394–395
Indyah SA, Timmerman H, Samhoedi M, Sastrohami D, Sugiyanto H, Goot H (2000) Synthesis of benzylideneacetophenones and their inhibition of lipid peroxidation. Eur J Med Chem 35:449–452
Jiaxi XU, Wang C, Zhang Q (2001) Synthesis of 1,3,3a,5-tetraaryl-3a,4,5,6-tetrahydro-3H-1,2,4-triazolo[4,3a][1,5]benzodiazepines. Heteroatom Chem 6:557–559
Kakati D, Sarma JC (2011) Microwave assisted solvent free synthesis of 1,3-diphenylpropenones. Chem Cent 5:1–8
Kappe OC, Dallinger D, Murphree S (2009) Practical microwave synthesis for organic chemists, 3rd edn. Wiley, Weinheim, p 192
Konovalov DA, Llewellyn LE, Heyden YV, Coomans DJ (2008) Robust cross-validation of linear regression QSAR models. Chem Inf Model 48:2081–2094
Koster RM (1959) Acetic acid for analgesic screening. Fed Proc 18:412–418
Kubiyini H (1995) In: Wolf M (ed) Burger’s medicinal chemistry and drug discovery, vol 1. Wiley, New York, pp 497–572
Kumar SK, Hager E, Catherine P, Gurulingappa H, Davidson NE, Khan SR (2003) Design, synthesis and evaluation of novel boronic-chalcone derivatives as antitumour agents. J Med Chem 46:2813–2815
Kumar PP, Prasad YR, Kumar PR, Rao AS (2008) Synthesis and antimicrobial activity of some new chalcones of 2-acetylpyridine. Eur J Chem 5:144–148
Liu M, Wilairat P, Go M (2001) Antimalarial alkoxylated and hydroxylated chalcones: structure–activity relationship analysis. J Med Chem 44:4443–4452
Mukherjee S, Kumar V, Prasad AK, Jain SC, Parmar VP (2001) Synthetic and biological activity evaluation studies on novel 1,3-diarylpropenones. Bioorg Med Chem 9:337–345
Nehad A, El-Latif A, El-Galil A, Amr E, Ibrahiem AA (2007) Synthesis, reactions and pharmacological screening of heterocyclic derivatives using nicotinic acid as a natural synthon. Monatshefte für Chemie 138:559–567
Nielsen SF, Christensen SB, Cruciani G, Kharazmi A, Liljefors T (1998) Antileishmanial chalcones: statistical design, synthesis and three-dimensional quantitative structure–activity relationship analysis. J Med Chem 41:4819–4832
OECD (2008) OECD Guidelines for the Testing of Chemicals Test No. 425: Acute oral toxicity—up and down procedure
Prasad YR, Prasoona L, Rao AL, Lakshmi K, Kumar PR, Rao BG (2005) Synthesis and antidepressant activity of some 1,3,5-triphenyl-2-pyrazolines and 3-(2″-hydroxy naphthalen-1″-yl)-1,5-diphenyl-2-pyrazolines. Int J Chem Sci 4:685–689
Ravichandran S, Karthikeyan E (2011) Microwave synthesis—a potential tool for green chemistry. Int J Chem Tech Res 3:466–470
Roy PP, Paul S, Mitra I, Roy K (2009) Two novel parameters for validation of predictive QSAR models. Molecules 14:1660–1701
Shibata K, Katsuyama I, Izoe H, Matsui M, Muramatsu H (1993) Synthesis of 4,6-disubstituted-2-methylpyridines and their 3-carboxamides. J Heterocycl Chem 30:277–281
Winter CA, Risely EA, Nuss GW (1962) Carrageenan induced oedema in hind paw of the rats as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med 111:541–552
Zhang XW, Zhao DH, Quan YC, Sun LP, Yin XM, Guan LP (2010) Synthesis and evaluation of anti-inflammatory activity of substituted chalcone derivatives. Med Chem Res 19:403–412
Acknowledgments
Authors take this opportunity to thank All India Council of Technical Education for funding this project. Authors also thank Dr. Mobin Khan, Vice President, Glen mark Pharmaceuticals Ltd., Mumbai, India, for recording the NMR spectra of the synthesized compounds. Authors are also thankful to Dr. Joag, Director, M. K. Ranganekar Memorial Drug Testing and Training Laboratory, Mumbai, India, for recording the IR spectra of the synthesized compounds.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vaidya, S.S., Vinaya, H. & Mahajan, S.S. Microwave-assisted synthesis, pharmacological evaluation, and QSAR studies of 1,3-diaryl-2-propen-1-ones. Med Chem Res 21, 4311–4323 (2012). https://doi.org/10.1007/s00044-012-9969-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-012-9969-1