Author(s):
Ashish Srivastava, Ashutosh Mishra, A. K. Rai
Email(s):
srivastava457@gmail.com
DOI:
10.5958/0974-360X.2020.00379.0 
Address:
Ashish Srivastava1, Ashutosh Mishra2, A. K. Rai1
1Department of Medicinal Chemistry, Institute of Pharmacy, Pranveer Singh Institute of Technology, Kanpur-209305, Uttar Pradesh, India.
2Acharya Narendra Dev College of Pharmacy, Babhnan, Gonda-271313, Uttar Pradesh, India.
*Corresponding Author
Published In:
Volume - 13,
Issue - 5,
Year - 2020
ABSTRACT:
Objective: Synthesis and Evaluation of Ulcerogenic potential for NSAID-Alendronate based prodrug. Methods: Three NSAIDs (Diclofenac, Indomethacin and Ibuprofen) were conjugated with Alendronate though amide linkage. The synthesized prodrugs were evaluated for their ulcerogenic potential on wistar rats at the dose of 25, 50 and 100mg/kg. Results: The severity index for the group administered with the parent drugs was in the range of ~ 1-2.7. However, the severity index for the group administered with the prodrug was in the range of ~0.5 to 1.8. Conclusion: The newly reported prodrugs showed significantly less signs of ulcerogencity.
Cite this article:
Ashish Srivastava, Ashutosh Mishra, A. K. Rai. Synthesis, Characterization and Evaluation of Ulcerogenic potential for NSAIDs-Alendronate based prodrug. Research J. Pharm. and Tech 2020; 13(5): 2107-2111. doi: 10.5958/0974-360X.2020.00379.0
Cite(Electronic):
Ashish Srivastava, Ashutosh Mishra, A. K. Rai. Synthesis, Characterization and Evaluation of Ulcerogenic potential for NSAIDs-Alendronate based prodrug. Research J. Pharm. and Tech 2020; 13(5): 2107-2111. doi: 10.5958/0974-360X.2020.00379.0 Available on: https://rjptonline.org/AbstractView.aspx?PID=2020-13-5-9
REFERENCES:
1. Zarghi A, Arfaei S. Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships. Iran J Pharm Res. 2011;10(4):655-83.
2. Piazza GA, Keeton AB, Tinsley HN, Whitt JD, Gary BD, Mathew B, et al. NSAIDs: Old Drugs Reveal New Anticancer Targets. Pharmaceuticals. 2010;3(5):1652-67.
3. Gurpinar E, Grizzle WE, Piazza GA. NSAIDs Inhibit Tumorigenesis, but How? Clin Cancer Res. 2014;20(5):1104.
4. Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JMW. How to diagnose rheumatoid arthritis early: A prediction model for persistent (erosive) arthritis. Arthritis Rheum. 2002;46(2):357-65.
5. Center J, Beange H, McElduff A. People with Mental Retardation Have an Increased Prevalence of Osteoporosis: A Population Study. Am J Ment Retard. 1998;103(1):19-28.
6. Guidelines ACoRSoRA. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum. 2002; 46(2): 328-46.
7. Suri S, Mönkkönen J, Taskinen M, Pesonen J, Blank MA, Phipps RJ, et al. Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity. Bone. 2001;29(4):336-43.
8. Lowe CE, Depew WT, Vanner SJ, Paterson WG, Meddings JB. Upper Gastrointestinal Toxicity of Alendronate. Am J Gastroenterol. 2000;95(3):634-40.
9. Etminan M, Lévesque L, Fitzgerald JM, Brophy JM. Risk of upper gastrointestinal bleeding with oral bisphosphonates and non steroidal anti-inflammatory drugs: a case-control study. Aliment Pharmacol Ther. 2009;29(11):1188-92.
10. Saxena V, Panicucci R, Joshi Y, Garad S. Developability assessment in pharmaceutical industry: An integrated group approach for selecting developable candidates. J Pharm Sci. 2009;98(6):1962-79.
11. Kerns EH. High throughput physicochemical profiling for drug discovery. J Pharm Sci. 2001;90(11):1838-58.
12. Jana S, Mandlekar S, Marathe P. Prodrug Design to Improve Pharmacokinetic and Drug Delivery Properties: Challenges to the Discovery Scientists. Curr Med Chem. 2010;17(32):3874-908.
13. Fang H, Kaur G, Wang B. Functional Group Approaches to Prodrugs: Functional Groups in Peptides. In: Stella VJ, Borchardt RT, Hageman MJ, Oliyai R, Maag H, Tilley JW, editors. Prodrugs: Challenges and Rewards Part 1. New York, NY: Springer New York; 2007. p. 965-88.
14. Rautio J, Kumpulainen H, Heimbach T, Oliyai R, Oh D, Järvinen T, et al. Prodrugs: design and clinical applications. Nat Rev Drug Discovery. 2008;7:255.
15. Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther. 2013;15 Suppl 3(Suppl 3):S3-S.
16. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res, Clin Gastroenterol. 2010;24(2):121-32.
17. Halen PK, Murumkar PR, Giridhar R, Yadav MR. Prodrug Designing of NSAIDs. Mini-Rev Med Chem. 2009;9(1):124-39.
18. Qandil AM. Prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), More Than Meets the Eye: A Critical Review. Int J Mol Sci. 2012;13(12):17244-74.
19. Shanbhag VR, Michael Crider A, Gokhale R, Harpalani A, Dick RM. Ester and Amide Prodrugs of Ibuprofen and Naproxen: Synthesis, Anti-inflammatory Activity, and Gastrointestinal Toxicity. J Pharm Sci. 1992;81(2):149-54.
20. Vachal P, Hale JJ, Lu Z, Streckfuss EC, Mills SG, MacCoss M, et al. Synthesis and Study of Alendronate Derivatives as Potential Prodrugs of Alendronate Sodium for the Treatment of Low Bone Density and Osteoporosis. J Med Chem. 2006;49(11):3060-3.
21. Vepsalainen JJ. Bisphosphonate Prodrugs. Curr Med Chem. 2002;9(12):1201-8.
22. Guénin E, Monteil M, Bouchemal N, Prangé T, Lecouvey M. Syntheses of Phosphonic Esters of Alendronate, Pamidronate and Neridronate. Eur J Org Chem. 2007;2007(20):3380-91.
23. Kolehmainen E, Tamminen J, Lappalainen K, Torkkel T, Seppälä R. Substituted Methyl 5β-Cholan-24-oates; Part III: Synthesis of a Novel Cholaphane from Ethylene Glycol Diester of Lithocholic Acid by Cyclization with Terephthalic Acid. Synthesis. 1996;1996(09):1082-4.
24. Giammei AJoMRopr. Bisphosphonate Prodrugs Utilizing Endogenous Carriers. The JYX publication archive of the University of Jyväskylä: University of Jyväskylä; 2016.
25. Elsaman T, Aldeeb OAA, Aboul-Fadl T, Hamedelneil EI. Synthesis, characterization and pharmacological evaluation of certain enzymatically cleavable NSAIDs amide prodrugs. Bioorganic Chemistry. 2017;70:144-52.
26. Kulwinder Singh, Monika, Neelam Verma. Gastrointestinal and Cardiovascular Risks of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Time to Translate Knowledge into Practice. Research J. Pharm. and Tech. 7(5): May, 2014; Page 575-580.
27. V. I. Strukov, A. I. Kislov, N. V. Eremina, G. P. Deriabina, M. Yu. Sergeeva-Kondrachenko, A. Yu. Antropov, Ya. V. Kuzmina, K. R. Tayrova, E. V. Petrova8, D. G. Elistratov, O. V. Strukova-Jones. The use of Bone Tissue Non-Steroid Anabolizators in Treatment of Osteoporosis. Research J. Pharm. and Tech. 2019; 12(5):2195-2199.
28. Padmanabhan. K, Jibi Paul, Sudhakar. S, Senthil Selvam. P, Sathya Priya. V, Veena Kirthika. S. Which is more prevalent among the female population - Osteopenia or Osteoporosis? A cross sectional study. Research J. Pharm. and Tech. 2019; 12(3): 1163-1168.
29. Bhagyashri T. Sakat, R B. Sakhare, U C. Suryvanshi, P. S. Kore, . S. K. Mohite, . C. S. Magdum. Osteoporosis: The Brittle Bone. Asian J. Pharm. Res. 2018; 8(1):39-43.
30. Ghanshyam Dhalendra, Trilochan Satapathy, Amit Roy. Animal Models for Inflammation: A Review. Asian J. Pharm. Res. 3(4): Oct. - Dec.2013; Page 207-212.
31. Monika Gaba, Punam Gaba, Sarbjot Singh, Neelima Dhingra. Inhibition of LFA-1/ICAM-1 Interaction: A Therapeutic Strategy for Surmounting Inflammation. Asian J. Pharm. Res. 5(1): Jan.-Mar. 2015; Page 37-47.
32. Nitin Mahurkar, Sayeed ul hasan S.M. Antiulcer Activity of Commicarpus chinensis in Ethanol and Aspirin Induced Ulcers. Asian J. Pharm. Res. 4(3): July-Sept. 2014; Page 119-122.
33. Nitin Mahurkar, S.M. Sayeed ul hasan. Synergistic Antiulcer Effect of Melatonin and Esomeprazole Combination in Pylorus Ligation, Ethanol, Aspirin induced Peptic Ulcers. Asian J. Pharm. Res. 5(1): Jan.-Mar. 2015; Page 10-14.
34. El harti Jaouad, Ansar M’hammed, Lmimouni Badr, Benomar Ali, Taoufik Jamal. Synthesis and Scolicidal Activity of some Potential Prodrugs of Albendazole. Research J. Pharm. and Tech. 5(11): Nov. 2012; Page 1442-1445.
35. Kalyani Dewangan, Kushagra Nagori, Mukesh Sharma, Ajay Singh, Sandhya Chandrakar, Vandana Devi Sahu, Garima Sharma, Sujata Gupta, Harsha Solanki, Manisha Majumdar, D. K. Tripathi, Amit Alexander, Ajazuddin. Formulation, evaluation and release studies of Indomethacin Suppositories. Research J. Pharm. and Tech. 2016; 9(7):942-944.
36. Arfeen M, Bhagat S, Patel R, Prasad S, Roy I, Chakraborti AK, et al. Design, synthesis and biological evaluation of 5-benzylidene-2-iminothiazolidin-4-ones as selective GSK-3β inhibitors. Eur J Med Chem. 2016 Oct 4;121:727–36.
37. Bhagat S, Arfeen M, Adane L, Singh S, Singh PP, Chakraborti AK, et al. Guanylthiourea derivatives as potential antimalarial agents: Synthesis, in vivo and molecular modelling studies. Eur J Med Chem. 2017 Jul 28;135:339–48.
38. Bhagat S, Arfeen M, Das G, Ramkumar M, Khan SI, Tekwani BL, et al. Design, synthesis and biological evaluation of 4-aminoquinoline-guanylthiourea derivatives as antimalarial agents. Bioorg Chem. 2019 Oct 1;91:103094.