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Synthesis and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan as gastrosparing NSAIDS

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Abstract

Synthesis, physicochemical characterization and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan have been attempted to develop novel gastrosparing NSAIDs, devoid of ulcerogenic side effects. The structures of synthesized prodrugs were confirmed by IR, 1H NMR, 13C NMR and mass spectroscopy. The hydrolysis kinetics studies were performed in simulated gastric fluid, simulated intestinal fluid and rat fecal matter. Its anti-inflammatory and ulcer index were analyzed along with estimation of biochemical parameters (GWM and Hexosamine), oxidative parameters (LPO, GSH, CAT, and SOD) and protein estimation. The results indicated that the synthesized prodrugs are chemically stable, biolabile and possesses optimum lipophilicity. They also exhibited retention of anti-inflammatory activity with reduced ulcerogenicity. The study showed that the mutual prodrugs are better in action compared to the parent drug and have fewer gastrointestinal side effects.

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Acknowledgments

The authors express their thanks to M/s. Alkem Laboratories, Mumbai, India, for providing gift sample of aceclofenac. The authors are grateful to Mr. P. Unneen, M.D., Alshifa College of Pharmacy, Perinthalmanna, kerala, India, for providing the necessary facilities to carry out this work.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Alshifa College of Pharmacy, Kizhattoor, Poonthavanam P.O., Perinthalmanna, Malappuram, Kerala, India

    Arun Rasheed, G. Lathika, K. P. Mansoor, A. K. Azeem & Nija Balan

  2. Department of Pharmaceutics, Sri Padmavathy School of Pharmacy, Mohans Garden, Tirupati, Andhra Pradesh, India

    Y. Prasanna Raju

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  1. Arun Rasheed
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  2. G. Lathika
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  4. K. P. Mansoor
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  5. A. K. Azeem
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  6. Nija Balan
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Correspondence to Arun Rasheed.

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Rasheed, A., Lathika, G., Raju, Y.P. et al. Synthesis and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan as gastrosparing NSAIDS. Med Chem Res 25, 70–82 (2016). https://doi.org/10.1007/s00044-015-1469-7

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