Chemical Characterization and Pharmacological Evaluation of Phytophenols-Etodolac Mutual Prodrugs
DOI:
https://doi.org/10.31351/vol32iss3pp49-59Keywords:
Mutual Prodrugs, Phytophenols, Etodolac, Anti-inflammatory, Analgesic, UlcerogenicAbstract
Etodolac is choice of drug for pain and inflammation but has major side effects of gastric ulcers that are due to free carboxylic group. Etodolac belongs to the chemical class of non-selective COX-inhibitor but preferentially COX-2 inhibitor. Here the ester linked mutual prodrugs of etodolac with phytophenols like vanillin, carvacrol, umbelliferone, guaiacol, sesamol and syringaldehyde were synthesized. All the prodrugs were characterized by IR-spectroscopy, 1H-NMR, 13C-NMR and mass spectrometry. Among the synthesized prodrugs, the Eto-van, Eto-umbe, Eto-sesa and Eto-syr showed improved analgesic and anti-inflammatory activity compared to etodolac. All the synthesized prodrugs showed less ulcerogenic side effects compared to etodolac.
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Nirmal NP, Rajput MS, Sarkar PD, Sinha S, Gupta A. Amino acid esters as prodrugs of an arylalkanoic acid COX inhibitor: Synthesis and biopharmaceutical and pharmacological evaluation. J Taibah Univ Sci [Internet]. 2015;9(4):455–64. Available from: http://dx.doi.org/10.1016/j.jtusci.2014.11.005
Toledo M V, Jose C, Suster CRL, Collins S E, Portela R, Banares M A, et al. Catalytic and molecular insights of the esterification of ibuprofen and ketoprofen with glycol. Molecular Catalysis. 2021; 513, 111811.
Kapoor B, Gulati M, Singh S K, Khatik G L, Gupta R, Kumar R, et al. Fail-safe nano-formulation of prodrug of sulfapyridine: Preparation and evaluation for treatment of rheumatoid arthritis. Material Science and Engineering C. 2021; 118, 111332.
Ribeiro H, Rodrigues I, Napoleao N, Lira L, Marques D, Verissimo M, et al. non-steroidal anti-inflammatory drugs (NSAIDs), pain and aging; Adjusting prescription to patient features. Biomedicine and Pharmacotherapy. 2022; 150, 112958.
Bindu S, Mazumder S, Bandyopadhyay. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochemical Pharmacology. 2020; 180, 114147.
Kuczynska J, Nieradko-Iwanicka B. Future prospects of ketoprofen in improving the safety of the gastric mucosa. Biomedicine and Pharmacotherapy. 2021; 1319, 111608.
Li Y, Li L, Jin Q, Liu T, Sun J, Wang Y, et al. Impact of the amount of PEG on prodrug nanoassemblies for efficient cancer therapy. Asian Journal of Pharmaceutical Sciences. 2022; 17, 241-252.
Hussain M A, Shad I, Malik, Amjad F, Kausar T, Kamran, et al. Hydroxypropylcellulose-flurbiprofen conjugates: design, characterization anti-inflammatory activity and enhanced bio-availability. Saudi Pharmaceutical Journal. 2020; 28, 869-875.
Liu W, Li Y, Yue Y, Zhang K, Chen Q, Wang H, et al. Synthesis and biological evaluation of curcumin derivatives containing NSAIDs for their anti-inflammatory activity.Bioorganic Med Chem Lett [Internet]. 2015;25(15):3044–51.
Kim WS, Kim K, Byun EB, Song HY, Han JM, Park WY, et al. RM, a novel resveratrol derivative, attenuates inflammatory responses induced by lipopolysaccharide via selectively increasing the Tollip protein in macrophages: A partial mechanism with therapeutic potential in an inflammatory setting. Int Immunopharmacol [Internet]. 2020;78(August 2019):106072.
Qiu L, Xu J, Ahmed K S, Zhu M, Zhang Y, Long M, et al. Stimuli-responsive, dual function prodrug encapsulated in hyaluronic acid micelles to overcome doxorubicin resistance. Acta Biomaterialia. 2022; 140, 686-699.
Krishna G, Shah K. Current drifts in design and development of prodrugs. ECS Trans. 2022, 107(1), 18939.
Halen P, Murumkar P, Giridhar R, Yadav M. Prodrug Designing of NSAIDs. Mini-Reviews Med Chem. 2008;9(1).
Hassib ST, Hassan GS, El-Zaher AA, Fouad MA, Abd El-Ghafar OA, Taha EA. Synthesis and biological evaluation of new prodrugs of etodolac and tolfenamic acid with reduced ulcerogenic potential. Eur J Pharm Sci. 2019;140.
Madhukar M, Sawraj S, Sharma PD. Design, synthesis and evaluation of mutual prodrug of 4-biphenylacetic acid and quercetin tetramethyl ether (BPA-QTME) as gastrosparing NSAID. Eur J Med Chem. 2010;45(6).
Manon B, Sharma PD. Design, synthesis and evaluation of diclofenac-antioxidant mutual prodrugs as safer NSAIDs. Indian J Chem - Sect B Org Med Chem. 2009;48(9).
Savjani JK, Mulamkattil S, Variya B, Patel S. Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents. Eur J Pharmacol [Internet]. 2017;801(February):28–34.
Al Asmari A, Al Shahrani H, Al Masri N, Al Faraidi A, Elfaki I, Arshaduddin M. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation. Toxicol Reports. 2016;3:105–13.
Abo-youssef AM. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats. Beni-Suef Univ J Basic Appl Sci [Internet]. 2016;5(2):187–92.
Elshaer M, Chen Y, Wang XJ, Tang X. Resveratrol: An overview of its anti-cancer mechanisms. Life Sci. 2018;207(May):340–9.
Ozturk H, Cetinkaya A, Duzcu SE, Tekce BK, Ozturk H. Carvacrol attenuates histopathogic and functional impairments induced by bilateral renal ischemia/reperfusion in rats. Biomed Pharmacother [Internet]. 2018;98(December 2017):656–61
Jia R, Li Y, Cao L, Du J, Zheng T, Qian H, et al. Antioxidative, anti-inflammatory and hepatoprotective effects of resveratrol on oxidative stress-induced liver damage in tilapia (Oreochromis niloticus). Comp Biochem Physiol Part - C Toxicol Pharmacol [Internet]. 2019;215(October 2018):56–66
Shah K, Gupta JK, Chauhan NS, Upmanyu N, Shrivastava SK, Mishra P. Prodrugs of NSAIDs: A Review. Open Med Chem J. 2017;11(1).
Puris E, Gynther M, Huttunen J, Auriola S, Huttunen KM. L-type amino acid transporter 1 utilizing prodrugs of ferulic acid revealed structural features supporting the design of prodrugs for brain delivery. Eur J Pharm Sci [Internet]. 2019;129(January):99–109.
Rasheed A, Lathika G, Raju YP, Mansoor KP, Azeem AK, Balan N. Synthesis and pharmacological evaluation of mutual prodrugs of aceclofenac with quercetin, vanillin and l-tryptophan as gastrosparing NSAIDS. Med Chem Res. 2016;25(1):70–82.
Fadl TA, Omar FA. Paracetamol (acetaminophen) esters of some non-steroidal anti- inflammatory carboxylic acids as mutual prodrugs with improved therapeutic index. Inflammopharmacology. 1998;6(2).
Kour J, Kumari N, Sapra B. Ocular prodrugs: Attributes and challenges. Asian Journal of Pharmaceutical Sciences. 2021, 16, 175-191.
Choudhary D, Goykar H, and Kalyane D, et al. Chapter 6- Prodrug design for improving the biopharmaceutical properties of therapeutic drugs. 2020; 179-226.
Shah K, Shrivastava SK, Mishra P. Synthesis, kinetics and pharmacological evaluation of mefenamic acid mutual prodrug. Acta Pol Pharm - Drug Res. 2013;70(5).
Haricharan Raju CM, Anand CV, Dubey PK, Acharyulu PVR. Alterntnate routes for the synthesis of ibuprofen piconol. Indian J Chem - Sect B Org Med Chem. 2007;46(1).
Paliwal M, Sucheta, Ruchita, Jain S, Monika, Himanshu. Synthesis and Biological Evaluation of Mutual Prodrugs of Carboxylic Group Containing Some Non-Steroidal Anti-Inflammatory Drugs and Propyphenazone. Curr Drug Deliv. 2017;14(8).
Shah K, Mujwar S, Krishna G, Gupta JK. Computational design and biological depiction of novel naproxen derivative. Assay Drug Dev Technol. 2020;18(7).
Jilani JA, Pillai GK, Salem MS, Najib NM. Evaluation of hydroxyethyl esters of mefenamic acid and diclofenac as prodrugs. Drug Dev Ind Pharm. 1997;23(3).
Singh R, Kumar V, Bharate SS, Vishwakarma RA. Synthesis, pH dependent, plasma and enzymatic stability of bergenin prodrugs for potential use against rheumatoid arthritis.Bioorganic Med Chem [Internet]. 2017;25(20):5513–21.
Khatavkar UN, Belsara DP. Synthesis and evaluation of glycolamide esters of diclofenac and mefenamic acid. Indian Drugs. 2002;39(7).
Ghodeswar BC, Pophalikar RN, Bhojani MR, Nagpal D, Dhaneshwar SS. Synthesis and pharmacological evaluation of mutual prodrugs of some nonsteroidal antiinflammatory drugs with glucosamine. Indian J Pharm Sci. 2004;66(6).
Suhas R, Gowda DC. Design and synthesis of tryptophan containing peptides as potential analgesic and anti-inflammatory agents. J Pept Sci. 2012;18(8):535–40.
Dhaneshwar S, Sutar A, Kadam P. Reducing ulcerogenic potential of biphenyl aceticacid:Design and development of chimeric derivatives with amino acids. J Saudi Chem Soc [Internet]. 2016;20:S211–20.
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