Design and synthesis of ibuprofen-quinoline conjugates as potential anti-inflammatory and analgesic drug candidates

Amany M. Ghanim, Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA; Department of Pharmaceutical Organic Chemistry Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt.
Adel S. Girgis, Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
Benson M. Kariuki, School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK.
Nermin Samir, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Mona F. Said, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Anwar Abdelnaser, Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, Egypt.
Soad Nasr, Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, Egypt; Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, D-89081 Ulm, Germany.
Mohamed S. Bekheit, Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
Mohamed F. Abdelhameed, Pharmacology Department, National Research Centre, Dokki, Giza 12622, Egypt.
Ahmad J. Almalki, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Tarek S. Ibrahim, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Siva S. Panda, Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA. Electronic address: sipanda@augusta.edu.

Author's Department

Institute of Global Health & Human Ecology

Fifth Author's Department

Institute of Global Health & Human Ecology

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https://doi.org/10.1016/j.bioorg.2021.105557

All Authors

Amany M. Ghanim, Adel S. Girgis, Benson M. Kariuki, Nermin Samir, Mona F. Said, Anwar Abdelnaser, Soad Nasr, Mohamed S. Bekheit, Mohamed F. Abdelhameed, Ahmad J. Almalki, Tarek S. Ibrahim, Siva S. Panda

Document Type

Research Article

Publication Title

Bioorganic chemistry

Publication Date

2-1-2022

doi

10.1016/j.bioorg.2021.105557

Abstract

A new set of ibuprofen-quinoline conjugates comprising quinolinyl heterocycle and ibuprofen moieties linked by an alkyl chain were synthesized in good yields utilizing an optimized reaction procedure in a molecular hybridization approach to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. The synthesized conjugates were screened for their anti-inflammatory, and ulcerogenic properties. Several conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test without showing any ulcerogenic liability. In addition, most conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate test. The most promising conjugates were the unsubstituted and 6-substituted fluoro- and chloro-derivatives of 2-(trifluoromethyl)quinoline linked to ibuprofen by a propyl chain. Their anti-inflammatory activity was evaluated against LPS-stimulated inflammatory reactions in RAW264.7 mouse macrophages. In this regard, it was found that most of the conjugates were able to significantly reduce the release and production of nitric oxide in the LPS-stimulated macrophages. The secretion and expression of the pro-inflammatory cytokines IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) were also significantly suppressed.

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105557

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105557

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