Pharmacokinetic evaluation and in vivo anti-inflammatory potential of cyanoacetate derivatives of succinimide
The purpose of the study is to evalute the in vivo anti -inflammatory activity of newly synthesized cyanoacetate derivatives of succinimides (C-23, C-31, and C-44) and to elucidate their possible mechanisms of action through key inflammatory mediator pathways. Anti-inflammatory activity was assessed using carrageenan-induced paw oedema and arachidonic acid-induced ear oedema models in vivo. Mechanistic involvement was investigated through histamine-, prostaglandin-, leukotriene-, and bradykinin-induced paw oedema assays. In silico ADME studies were performed to predict pharmacokinetic properties and metabolic interactions. All tested compounds exhibited significant anti-inflammatory activity, with C-44 showing the highest potency. Mechanistic studies indicated that the anti-inflammatory effects were predominantly mediated via inhibition of prostaglandin and leukotriene pathways. ADME predictions suggested high gastrointestinal absorption, favourable oral bioavailability, and minimal interaction with major metabolic enzymes. The synthesized cyanoacetate derivatives, particularly C-44, demonstrate promising anti-inflammatory potential with favourable pharmacokinetic profiles, supporting their candidacy for further development as effective anti-inflammatory agents.
Authors
- Abdullah S. M. Aljohani (ORCID: https://orcid.org/0000-0003-4017-7698)
- Marcello Iriti (ORCID: https://orcid.org/0000-0002-5063-1236)
- Waleed Al Abdulmonem (ORCID: https://orcid.org/0000-0003-2984-9262)
- Aini Pervaiz
- Wadood Ali Shah
- Abdur Rauf (ORCID: https://orcid.org/0000-0003-2429-5491)
- Bushra Ansari
- Muhammad Saeed Jan (ORCID: https://orcid.org/0000-0003-2411-6510)
- A Khan
- Imad Ahmad
- Syed Muhammad Mukarram Shah
Institutions
- Bacha Khan University (PK)
- Qassim University (SA)
- Government of Khyber Pakhtunkhwa (PK)
- University of Campania "Luigi Vanvitelli" (IT)
- University of Swabi (PK)
- National Interuniversity Consortium of Materials Science and Technology (IT)
- University of Malakand (PK)
Publication Details
- Journal
- Naunyn-Schmiedeberg s Archives of Pharmacology
- Published
- 2026-07-22
- DOI
- https://doi.org/10.1007/s00210-026-05720-z
- Primary Topic
- Synthesis and biological activity
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Università degli Studi di Milano