Synthesis and antimicrobial activity of Ibuprofen derivatives

Abstract

In order to reduce the ulcerogenic effect of ibuprofen, its carboxylic group has been converted into 5-membered and 6-membered heterocyclic rings. Various 1,3,4-thiadaizo (y), imidazo [2,1-b] [1,3,4] thiadiazoles (1a-d), 1,3-oxazin-2-yl (2), quinazolin-2-yl (3, 4 and 5), hydrazine, pyrazole (6), pyrazone (7, 8) and oxadiazole (9, 12). Derivatives of ibuprofen were prepared by cyclization under various reaction conditions in a very good yield. The microbial inhibitory effect of the new agents has been assessed in vitro against Gram-positive and Gram-negative bacteria activity. Compounds (4, 5, and 8) showed the highest antibacterial activities compared to other compounds and standard drugs. However, compound (1b) showed the lowest antibacterial activity compared to other compounds. All compounds have been characterized by IR, 1H NMR and C.H.N analysis.

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Abdulla, I. (2014) Synthesis and antimicrobial activity of Ibuprofen derivatives. Natural Science, 6, 47-53. doi: 10.4236/ns.2014.62008.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Bradbury, F. (2004) How important is the role of the physician in the correct use of a drug? An observational cohort study in general practice. International Journal of Clinical Practice, 144, 27-32.
[2] Tripathi, K.D. (2003) Non-steroidal anti-inflammatory drugs and anti-pyretic analgesics. Essentials of medical pharmacology. 5th Edition, Jaypee Brothers, New Delhi.
[3] Bushra, R. and Aslam, N. (2010) An overview of clinical pharmacology of Ibuprofen. Oman Medical Journal, 25, 155-1661.
[4] Riley, T.R. and Smith, J.P. (1998) Ibuprofen-induced hepatotoxicity in patients with chronic hepatitis C: A case series. American Journal of Gastroenterology, 93, 15631565.
[5] Potthast, H., Dressman, J.P., Junginger, H.E., Midha, K.K., Oeser, H., Shah, V.P., Vogelpoel, H. and Barends, D.M. (2005) Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ibuprofen. Journal of Pharmaceutical Science, 94, 10.
[6] Warner, T.D., Giuliano, F., Vaynovie, I., Bukasa, A., Mitche J.A. and Vave, J.R. (1999) Non-steroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastro intestinal toxicity a full in vitro analysis. Proceedings of National Academy Science of USA, 96, 7563-7568.
[7] Tan, S.C., Patel, B.K., Jackson, S.H., Swift, C.G. and Hutt, J.A. (2002) Stereoselectivity of ibuprofen metabolism and pharmacokinetics following the administration of the racemate to healthy volunteers. Xenobiotica, 32, 683-697.
[8] Mahammad, A. and Shikar K. (2007) Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of ibuprofen derivatives. Acta Pharmacy, 57, 31-45.
[9] Demirbas, A., Sahin, D., Demirbas, N. and Karaoglu, S.A. (2009) Synthesis of some new 1,3,4-thiadiazol-2-ylmethyl-1,2,4-triazole derivatives and investigation of their antimicrobial activities. European Journal of Medical Chemistry, 44, 2896-2903.
[10] Radi, M., Crespan, E., Botta, G., Falchi, F., Maga, G., Manetti, F., Corradi, V., Mancini, M., Santucci, M.A., Schenone, S. and Bott, M. (2008) Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents. Bioorganic & Medicinal Chemistry Letters, 18, 1207-1211.
[11] Al-Omar, M., Al-Deeb, O.A., Al-Khamees, H.A. and ElEmam, A.A. (2004) 1,3,4-Thiadizoles. Regioselective ODemethylation on Dehydrative Cyclization of 1-(3,4,5Trimethoxybenzoyl)-4-Substituted Thiosemicarbazides with Sulphuric Acid. Phosphorus Sulfur and Silicon, 179, 2509-2517.
[12] Gadad, A.K., Mahajanshetti, C.S., Nimbalkar, S. and Raichurkar, A. (2000) Synthesis and antibacterial activity of some 5-guanylhydrazone/thiocyanato-6-arylimidazo [2,1b]-1,3,4-thiadiazole-2-sulfonamide derivatives. European Journal of Medical Chemistry, 35, 853-857.
[13] Juddhawala, K.V., Parekh, M.N. and Rawal, B.M. (2011) Synthesis and antibacterial activities of N-chloro aryl acetamide substituted thaizole and 2, 4-thazolidinedione derivatives. A Chive of Applied Science Research, 3, 540548.
[14] Loana, V., Maria, R. and Oana, D. (2013) New derivatives of aryl-propionic acid. Syanthesis and biologlcal evaluation. Revista Medico-Chirurgicala a Societatii de Medici si Naturalisti din Iasi’s, 2, 532-537.
[15] Mohamed, S.K., Albayati, M., Omara, W.A.M., Abdelhamid, A.A., Potgeiter, H., Hameed, A.S. and Al-Janabi, K.M. (2012) Functionalization of ibuprofen core structure compound: Part 1 Synthesis of potential chemotherapeutic agents incorporated ibuprofen sub-structure and their in vitro antimicrobial study. Journal of Chemical and Pharmaceutical Research, 4, 3505-3517.

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