SYNTHESIS AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF NEW NAPROXEN ANALOGUES HAVING 1, 2, 4-TRIAZOLE-3-THIOL

Monther F. Mahdi; Noor H. Naser; Nethal H. Hammud

doi:10.22159/ijpps.2017v9i7.18273

Authors

Monther F. Mahdi Department of Pharmaceutical Chemistry, College of Pharmacy, Al- Mustansiriyia University, Baghdad, Iraq
Noor H. Naser Department of Pharmaceutical Chemistry, College of Pharmacy, Kufa University, Najaf, Iraq
Nethal H. Hammud Department of Pharmaceutical Chemistry, College of Pharmacy, Kufa University, Najaf, Iraq

DOI:

https://doi.org/10.22159/ijpps.2017v9i7.18273

Keywords:

Naproxen analogues, Synthesis of new naproxen derivatives, Triazole heterocyclic ring

Abstract

Objective: The objective of this search was to synthesize a new naproxen analogues having a 1,2,4-triazole-3-thiol heterocyclic ring, and preliminary pharmacological assessment of the anti-inflammatory activity of the synthesized compounds.

Methods: The synthesis of naproxen analogues that having 1,2,4-triazole-3-thiol heterocyclic ring occur through esterification of naproxen, and then its reaction with hydrazine hydrate, and carbon disulfide, finally different aromatic aldehydes reacted with triazole derivatives of naproxen containing amino group to produce schiff bases.

Results: In vivo acute anti-inflammatory activity of the synthesize compounds (Va-Vd) was evaluated in rats using egg-white induced edema model of inflammation in a dose equivalent to (50 mg/kg) of naproxen. All tested compounds were produced a significant reduction in paw edema with respect to the effect of propylene glycol 50% v/v (control group). Compound Vd produced superior anti-inflammatory activity compared to naproxen.

Conclusion: The results obtained in this work give evidence about the valid synthesis of 1,2,4 triazole-3-thiol derivatives of naproxen, which reacted with different aldehydes to yield several schiff bases. The incorporation of benzaldehyde possess para-electron donating group (para-hydroxyl benzaldehyde) will increase the anti-inflammatory activity of naproxen.

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References

Mohammed J, Dehghan M, Adil S. Enhancement of dissolution and anti-inflammatory effect of meloxicam using solid dispersions. Int J Appl Pharm 2010;2:22-7.

Prakash PR, Raghavendra Rao HG, Soujanya C. Formulation, evaluation, and anti-inflammatory activity of topical etoricoxib gel. Asian J Pharm Clin Res 2010;3:126-9.

Blanca-Lopez N, Cornejo-Garcia JA, Perez-Alzate D, Perez-Sanchez N, Plaza-Seron MC, DoÃ±a I, et al. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs in children and adolescents: Selective reactions. J Investig Allergol Clin Immunol 2015;25:385-95.

Ramakrishna S, Mihira V, Raja Vyshnavi K, Ranjith V. Design and evaluation of drug release kinetics of meloxicam sustained release matrix tablets. Int J Curr Pharm Res 2012;4:90-9.

Patel KM, Biswal B, Karna N, Patel J. Preparation and evaluation of sustained release indomethacin tablets using skimmed milk and povidone. Int J Pharm Res 2011:3:60-2.

Datar P, Shendge T. Design, synthesis and stability studies of mutual prodrugs of NSAIDâ€™s. Chem Informatics 2015;1:1-7.

Nicholas SK, Melissa VC, Anne KZ, Eliana GV, Jing J, Lisa MB, et al. Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-ÎºB and NFAT transcriptional pathways. PNAS 2016;113:434-9.

Rana K, Pandurangan A, Singh N, Tiwari AK. A systemic review of schiff bases as an analgesic, anti-inflammatory. Int J Curr Pharm Res 2012;4:5-11.

Modi CM, Mody SK, Patel HB, Dudhatra GB, Kumar A, Avale M. Toxicopathological overview of analgesic and anti-inflammatory drugs in animals. J Appl Pharm Sci 2012;2:149-57.

Lakshmi PK, Kumar MK, Sridharan A, Bhaskaran. Formulation and evaluation of ibuprofen topical gel: A novel approach for penetration enhancement. Int J Appl Pharm 2011:3:25-30.

Dixit M, Kulkarni PK, Gowtham V, Shivakumar HG. Preparation and characterization of spray dried microparticle and chilled spray dried particle of ketoprofen by spray drying method. Asian J Pharm Clin Res 2011;4:138-42.

Shaheed DQ, Mubarak AK, Libeg AA-A, Abbas HK, AL-Rekabi MD, Husssein AH. Design and synthesis of new derivatives of ketoprofen linked to natural antioxidants (thymol, menthol and guaiacol) as possible mutual prodrugs. World J Pharm Res 2015;4:310-9.

Reddy PS, Sait S, Hotha KK. Estimation of naproxen related substances in sumatriptan succinate and naproxen sodium tablets by UPLC. Asian J Chem 2013;25:9717-21.

Nissen SE, Yeomans ND, Solomon DH, LÃ¼scher TF, Libby P, Husni E, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med 2016;1:1-11.

Zarghi A, Arfaei S. Selective COX-2 inhibitors: a review of their structure-activity relationship. Iranian J Pharm Res 2011;10:655-83.

Abdulhadi SL, Qasir AJ, Abdul Razzak NA. Synthesis of new conjugates of some NSAIDs with sulfonamide as possible mutual prodrugs using tyrosine spacer for colon targeted drug delivery. Iraqi J Pharm Sci 2013;22:22-9.

Mistry BD, Desai KR, Intwala SM. Comparative studies of novel triazole derivative having a chiral center and their antimicrobial activities. Der Pharma Chem 2013;5:173-80.

Sweety D, Iqbal CM, Saravanan J, Mohan S. Synthesis and in vitro antimicrobial activity of some novel substituted 1, 3, 4-thiadiazoles. World J Pharm Res 2013;2:3199-208.

Christensen JB. A simple method for synthesis of active esters of isonicotinic and picolinic acids. Molecules 2001;6:47-51.

Jubie S, Sikdar P, Antony S, Kalirajan R, Gowramma B, Gomathy S, et al. Synthesis and biological evaluation of some schiff bases of [4-(amino)-5-phenyl-4H-1, 2, 4-triazole-3-thiol]. Pakis J Pharm Sci 2011;24:109-12.

Husain A, Naseer MA, Sarafroz M. Synthesis and anticonvulsant activity of some noval fused heterocyclic 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives. Acta Poloniae Pharm Drug Res 2009;66:135-40.

Zainab Hussain, Emad Yousif, Ahmed Ahmed, Ali Altaie. Synthesis and characterization of schiff's bases of sulfamethoxazole. Org Med Chem Lett 2014;4:1.

Mahdi MF, Raauf A-MR, Kadhim FA-H. Design, synthesis and acute anti-inflammatory evaluation of new non-steroidal anti-inflammatory agents having 4-thiazolidinone pharmacophore. J Nat Sci Res 2015;5:21-8.

Vogel HG, Goethe JH. Drug discovery and evaluation. Pharmacological assays. 2nd ed. Springer-Verlag. Berlin Heidelbers; 2002. p. 751.

Cram DJ, Hammond GS. Organic synthesis. 2nd ed. McGraw-Hill Book Company Inc; 1964. p. 561.

Jamal MY. Synthesis and preliminary antibacterial activity of some new schiff's base compounds derived from 5,5'-dimercapto-4,4'-diamin bis-1,2,4-triazole. Diala J 2008;27:71.

Xavier A, Srividhya N. Synthesis and study of schiff base ligands. J Appl Chem 2014;7:6-15.

Ravi V, Saleem TSM, Patel SS, Raamamurthy J, Gauthaman K. Anti-inflammatory effect of methanolic extract of Solanum nigrum Linn berries. Int J Appl Res Nat Prod 2009;2:33-6.