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Aceclofenac and Diclofenac Sodium Conjugates with Amino Acids to Overcome Acidity

Shuchi Jain, Amreen Khan, Paridhi Jain


This research work was based on a conjugate approach with some non-steroidal anti-inflammatory drugs (NSAIDs) to overcome the side effects like gastric irritation, solubility behavior, and some other effects of NSAIDs. Almost all the NSAIDs have undesirable reactions as well as they cause some types of major adverse reactions. Here the prodrugs conjugates are the approaches that increase the lipophilicity of the drug and decrease the solubility in water by decreasing the concentration gradient, by this absorption of the drug is controlled. We have synthesized some conjugated derivatives and all the derivatives were confirmed by TLC, solubility, partition coefficient, UV, and IR spectroscopy. This approach is used to increase the lipophilicity of those drugs which cause lower water solubility. These types of conjugates are prepared by a conventional method using N,N-dicyclo-hexyl carbodiimide, and this method is characterized by melting point, TLC, and UV and NMR spectroscopy methods. In this method, we found that aceclofenac conjugates have maximum water solubility and having less side effects. The partition coefficient seems to be more than that parent compound. So that the present work shows that the conjugates with amino acids were more water soluble and had stability in the given pH profile and in that pH, it shows an increased rate of hydrolysis. The results of the current study reveal that the amino acid-conjugated derivatives that were produced have increased water solubility. This method can be used in the future to reduce the side effects of additional NSAIDs and improve their solubility in water. In the future, this study must be concluded the mechanism of action and efficiency study of compounds on different animals.


Aceclofenac, diclofenac sodium, amino acids, prodrug, conjugates

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Pradip M, Lopamudra B, Agrawal RK. Some ibuprofen Derivatives for Improved analgesic and anti-inflammatory activities. Indian J Pharm Sci. 1989;51(1):11–3.

Analgesics anti-inflammatory and antipyretics. In: Parfitt K, editor. Martindale: the complete drug reference. 32nd ed. London: Pharmaceutical Press; 1999. p. 61–2.

Bakhle YS. COX-1 and COX-2: towards the development of more selective NSAIDs. Drug News Perspect. 1994;7:501–12.

Martindale W, Parfitt K. editors. Analgesics anti-inflammatory and antipyretics. In: Martindale: The Complete Drug Reference. 32nd ed. London: Pharmaceutical Press; 1999. p. 61–2.

Dalpiaz A, Pavan B, Scaglianti M, Vitali F, Bortolotti F, Biondi C, et al. Vitamin C and 6-amino-vitamin C conjugates of diclofenac: synthesis and evaluation. Int J Pharm. 2005 Mar 3;291(1–2):171–81. doi: 10.1016/j.ijpharm.2004.07.054.

Ettmayer P, Amidon GL, Clement B, Testa B. Lessons learned from marketed and investigational prodrugs. J Med Chem. 2004 May 6;47(10):2393–404. doi: 10.1021/jm0303812.

Hutchinson I, Jennings SA, Vishnuvajjala BR, Westwell AD, Stevens MF. Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl)

benzothiazole amino acid prodrugs. J Med Chem. 2002 Jan 31;45(3):744–7. doi: 10.1021/jm011025r.

Niethammer A, Gaedicke G, Lode HN, Wrasidlo W. Synthesis and preclinical characterization of a paclitaxel prodrug with improved antitumor activity and water solubility. Bioconjug Chem. 2001 May 16;12(3):414–20. doi: 10.1021/bc000122g.

Ghodeswar BC, Pophalikar RN, Bhojani MR, Nagpal D, Dhaneshwar SS. Synthesis and pharmacological evaluation of mutual prodrugs of some nonsteroidal anti-inflammatory drugs with glucosamine. Indian J Pharm Sci. 2004;66(6):773.

Nakamura J, Asai K, Nishida K, Sasaki H. A novel prodrug of salicylic acid, salicylic acid-glycylglycine conjugate, utilizing the hydrolysis in rabbit intestinal microorganisms. J Pharm Pharmacol. 1992 Sep;44(9):713–6. doi: 10.1111/j.2042–7158.1992.tb05505.x.


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