Non-carboxylic Analogues of Aryl Propionic Acid: Synthesis, Anti-inflammatory, Analgesic, Antipyretic and Ulcerogenic Potential

S. I. Eissa; A. M. Farrag; A. A. A. Galeel

doi:10.1055/s-0033-1363251

Drug Research, Table of Contents

Drug Res (Stuttg) 2014; 64(09): 485-492
DOI: 10.1055/s-0033-1363251

Original Article

Non-carboxylic Analogues of Aryl Propionic Acid: Synthesis, Anti-inflammatory, Analgesic, Antipyretic and Ulcerogenic Potential

S. I. Eissa

¹Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azher University, Nasr City,Cairo, Egypt

,

A. M. Farrag

¹Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azher University, Nasr City,Cairo, Egypt

,

A. A. A. Galeel

²Researcher, Pharmacology Department, National Research Center, Dokki, Cairo, Egypt

› Author Affiliations

Abstract

As a part of ongoing studies in developing new potent anti-inflammatory and analgesic agents, a series of novel 6-methoxy naphthalene derivatives was efficiently synthesized and characterized by spectral and elemental analyses. The newly synthesized compounds were evaluated for their anti-inflammatory activities using carrageenin-induced rat paw edema model, analgesic activities using acetic acid induced writhing model in mice and anti-pyretic activity using yeast induced hyperpyrexia method as well as ulcerogenic effects. Among the synthesized compounds, thiourea derivative (6a, e) exhibited higher anti-inflammatory activity than the standard drug naproxen in reduction of the rat paw edema (88.71, 89.77%) respectively. All of the non-carboxylic tested compounds were found to have promising anti-inflammatory, analgesic and antipyretic activity, while were devoid of any ulcerogenic effects.

Key words

naproxen - anti-inflammatory - analgesic - antipyretic - ulcer effect

Full Text

References

References
1 Amir M, Kumar S. Synthesis of some new 2-(2-fluro-4-biphenyl)propionic acid derivatives as potential anti-inflammatory agents. Pharmazie 2005; 60: 175-180
2 Amir M, Kumar H, Javed SA. Condensed bridgehead nitrogen heterocyclic system: Synthesis and pharmacological activities of 1, 2, 4-triazolo-[3, 4-b]-1, 3,4-thiadiazole derivatives of ibuprofen and biphenyl-4-yloxy acetic acid. Eur J Med Chem 2008; 43: 2056-2066
3 Halen PK, Murumer PR, Giridhar R et al. Prodrug designing of NSAIDs. Mini-Reviews in Med Chem 2009; 9: 124-139
4 Zarghi A, Ghodsi R, Aziz E et al. Synthesis and biological evaluation of new 4-carboxyl quinoline derivatives as cyclo-oxygenase-2 inhibitors. Bioorg & Med Chem 2009; 17: 5312-5317
5 Takeuchi K, Tanaka A, Kato S et al. Roles of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Clinica Chimica Acta 2010; 411: 459-466
6 Ishihara T, Tanaka K-I, Tashiro S et al. Protective effect of rebamipide against celecoxib-induced gastric mucosal cell apoptosis. Biochem Pharmacol 2010; 79: 1622-1633
7 Sostres C, Gargallo C, Arroyo MT et al. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Practice & Research Clinical.Gastroenterology 2010; 24: 121-132
8 Mahdi MF, Dawood AH, Hassan Ali M et al. Synthesis & Chemical Hydrolysis Study of some NSAIDs Linked to Natural Antioxidant via Alanine. J of Advances in Chem 2013; 4: 368-376
9 Sadek B, Hamruoni AM, Adem A. Anti-inflammatory agents of the carbamoylmethyl ester class: synthesis, characterization, and pharmacological evaluation. J Inflamm Res 2013; 6: 35-43
10 Omar TN-A. Synthesis and Preliminary Pharmacological Evaluation of Esters and Amides Derivatives of Naproxen as Potential Anti-Inflammatory Agents. Iraqi J Pharm Sci 2013; 22: 120-127
11 Vivekkumar Redasanil K, Bari SB. Synthesis and Evaluation of Glyceride Prodrugs of Naproxen. Open Journal of Medicinal Chemistry 2013; 3: 87-92
12 Di L, Xiao-hong Y, Wei S et al. Synthesis, crystal structure and biological activities of naproxen-eugenol ester prodrug. Chem Res in chin univ 2013; 29: 245-248
13 Ching-San L, Tingmin W. Modified forms of nonsteroidal antiinflammatory drugs (NSAIDs) having reduced side effects. US Pat Appl Publ 2003; 29 pp., Cont.-in-part of U.S. Ser. No. 97,197. CODEN: USXXCO US 2003220468 A1 20031127 CAN 140:737 AN 2003:931006 CAPLUS
14 Ebeid MY, AlAshmawi SE, Abbas SE et al. Synthesis and biological activity of certain ibuprofen derivatives. Egypt. J Pharm Sci 1989; 30: 389-398
15 Kalgutkar AS, Marnett AB, Crews BC et al. Ester and amide derivatives of the nonsteroidal anti-inflammatory drugs, indomethacin, as selective Cyclo-oxygenase-2 inhibitors. J Med Chem 2000; 43: 2860-2870
16 Shanbhag VR, Crider AM, Gokhale R et al. Ester and amide prodrugs of ibuprofen and naproxen: Synthesis, anti-inflammatory activity, and gastrointestinal toxicity. J Pharm Sci 1992; 81: 149-154
17 Kalgutkar AS, Crews BC, Scott W et al. Biochemically based design of cyclo-oxygenase-2 (COX-2) inhibitors: Facile conversion of nonsteroidal anti-inflammatory drugs to potent and highly selective COX-2 inhibitors. J Pharmacology 2000; 97: 925-930
18 Zuffanti S. Preparation of acyl chlorides with thionyl chloride. J Chem Educ 1948; 25: 481
19 Al-Sehemi AGM, El-Sharief AMSh, Ammar YA. Propionic acid in organic synthesis: Novel synthesis of benzimidazole, 3,1-benzoxazine, 3-aminoquinozoline and 3-amino[2,3]pyrimidine derivatives containing 2-naphthyl propionyl moiety. Ind J Chem Section B Org Chem Including Med Chem 2006; 45: 450-455
20 Khalifa M, Ismail MMF, Eissa S et al. Design and synthesis of novel 6-methoxynaphthalene derivatives with potential anticancer activity. Der Pharma Chemica 2012; 4: 1552-1566
21 Amir A, Oberoi A, Alam S. Synthesis and anti-inflammatory activity of some new 6-methoxy-α-methyl-2-naphthalene acetic acid derivatives. Ind J of Chem 1999; 38B: 237-239
22 Winter CA, Risley EA, Nuss GW. Carrageenan – induced edema in hind paw of rat as an assay for anti-inflammatory drugs. Proc Soc Expt Biol Med 1962; 111: 544-547
23 Khan H, Saeed M, Gilani AUH et al. Antinociceptive activity of Polygonatum verticillatum rhizomes in pain models. J Ethnopharmacol 2010; 127: 521-527
24 Abou Zeit-Har MS, Verimer T, Long JP. Effect of long term estrogen and lithium treatment on restraint induced gastric erosion in intact and ovariectomized rats. Pharmazie 1982; 37: 593-595
25 Sakandé J, Nacoulma OG, Nikièma JB et al. Etude de l’effetantipyrétique d’extraits des inflorescences males du rônier Borassus aethiopum Mart (Arecaceae). Med Afr Noire 2004; 51: 280-282
26 Ebeid MY, Al-Ashmawi SE, Abbas SE et al. Synthesis and biological activity of certain ibuprofen derivatives. Egypt. J Pharm Sci 1989; 30: 399-409
27 Nirmal R, Prakash CR, Meenakshi K. Shanmugapandiya, Young, P. Synthesis and pharmacological evaluation of novel Schiff base analogues of 3-(4-amino)phenylimino)5-fluroindolin-2-one. J Pharm 2010; 2: 162-168
28 Bhandari SV, Bothara GK, Patil AA et al. Design, synthesis and pharmacological screening of novel antihypertensive agents using hybrid approach. Bioorg Med Chem 2009; 17: 390-400
29 Chen J, Li J, Gue C et al. Discovering novel chemical inhibitors of human cyclophilin A; virtual screening, synthesis, and bioassay. Bioorg Med Chem 2006; 14: 2209-2224
30 Ismail MMF, Amin KM, Noman E et al. New quinoxaline 1,4-di-N-oxides: Anticancer and hypoxia-selective therapeutic agents. Eur J Med Chem 2010; 45: 2733-2738