Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of new 2-(4-isobutylphenyl)propanoic acid derivatives

Article abstract of DOI:10.3109/14756366.2011.578743

Synthesis and pharmacological evaluation of various 2-(4-isobutylphenyl) propanoic acid derivatives containing 1,3,4-thiadiazole and thiadiazolo[3,2-a] [1,3,5]triazine-5-thione nucleus is reported here. The structures of new compounds are supported by IR, ¹H & ¹³C NMR data. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA). Compound 4i and 5f showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid-induced writhings and 0.7 and 0.65 of severity index, respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen.

Full text of DOI:10.3109/14756366.2011.578743

Journal of Enzyme Inhibition and Medicinal Chemistry, 2012; 27(1): 110–116
© 2012 Informa UK, Ltd.
ISSN 1475-6366 print/ISSN 1475-6374 online
DOI: 10.3109/14756366.2011.578743
ReseaRch aRtIcle
Synthesis and evaluation of anti-inflammatory, analgesic,
ulcerogenic and lipid peroxidation properties of
new 2-(4-isobutylphenyl)propanoic acid derivatives
Jignesh Priyakant Raval1, Ankur Navinchandra Gandhi1, Tarunkumar Nanjibhai Akhaja1, Kruti
Navinbhai Myangar1, and Nilesh Hasmukhbhai Patel2
1Department of Pharmaceutical Chemistry, Ashok & Rita Patel Institute of Integrated Study and Research in
Biotechnology and Allied Sciences(ARIBAS), New Vallabh Vidyanagar, Gujarat, India and 2EMCURE Pharmaceuticals
USA INC, 21-B Cotters In, East Brunswick, NJ
abstract
Synthesis and pharmacological evaluation of various 2-(4-isobutylphenyl)propanoic acid derivatives containing
1,3,4-thiadiazole and thiadiazolo[3,2-a][1,3,5]triazine-5-thione nucleus is reported here. The structures of new
compounds are supported by IR, 1H & 13C NMR data. These compounds were tested in vivo for their anti-inflammatory
activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their
analgesic, ulcerogenic and lipid peroxidation activities. The compounds, which showed less ulcerogenic action, also
showed reduced malondialdehyde production (MDA). Compound 4i and 5f showed 89.50 and 88.88% of inhibition
in paw edema, 69.80 and 66.25% protection against acetic acid-induced writhings and 0.7 and 0.65 of severity index,
respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen.
Keywords: 2-(4-isobutylphenyl)propanoic acid, thiadiazolo[3;2-a][1;3;5]triazine-5-thione, anti-inflammatory,
analgesic, ulcerogenic, lipid peroxidation activities
Introduction
use of these NSAIDs, including ibuprofen, may elicit
Currently available non-steroidal anti-inflammatory
drugs (NSAIDs) like ibuprofen, diclofenac, indometha-
cin and flurbiprofen suffer from common drawback of
gastric toxicity due to free carboxylic acid group. Long-
term use of these drugs has been associated with gastro-
intestinal (GI) ulceration, bleeding and nephrotoxicity1.
e GI damage from NSAIDs is generally attributed to
two factors, local irritation by the carboxylic acid moiety,
common to most NSAIDs (topical effect), and decreased
tissue prostaglandin production, which undermines the
physiological role of cytoprotective prostaglandins in
maintaining the GI health and homeostasis2,3. e phar-
macological activity of NSAIDs is related to the suppres-
sion of prostaglandin biosynthesis from arachidonic
acid by inhibiting cyclooxygenases (COXs)2,4. Chronic
appreciable GI toxicity5; therefore, synthetic approaches
based upon NSAID’s chemical modification have been
undertaken with the aim of improving the NSAID safety
profile. Studies described that the derivatization of the
carboxylate function of representative NSAIDs resulted
in an increased anti-inflammatory activity with reduced
ulcerogenic effect6,7. Furthermore, certain compounds
bearing 1,3,4-thiadiazole, Schiff base and 1,3,5-triazine
nucleus have been reported to possess significant anti-
inflammatory activity8–12. In continuation to our earlier
work on novel pharmoclogical agent13–15, this time we
focus to discover new and useful agents for treating
inflammatory diseases, we have replaced the carboxylic
acid group of ibuprofen with 2-(1-(4–isobutylphenyl)
ethyl)–7–(substituted phenyl)-6,7–dihydro-5H-[1,3,4]
Address for Correspondence: Jignesh Priyakant Raval, Ashok & Rita Patel Institute of Integrated Studies & Research in Biotechnology and
Allied Sciences, Department of Pharmaceutical Chemistry, ADIT Campus, Behind Vithal Udhognagar, New Vallabh Vidyanagar, Gujarat,
India 388121. E-mail: drjpraval@yahoo.co.in
(Received 01 March 2011; revised 27 March 2011; accepted 04 April 2011)
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