A new cationic palladium(II) dithiocarbamate exhibits anti-inflammatory, analgesic, and antipyretic activities through inhibition of inflammatory mediators in in vivo models

  • Muhammad Naveed
  • Shahan Zeb Khan
  • Sara Zeeshan
  • Adnan Khan
  • Bushra Shal
  • Ayesha Atiq
  • Hussain Ali
  • Rahim Ullah
  • Zia-ur-RehmanEmail author
  • Salman KhanEmail author
Original Article


Inflammation is being a protective mechanism of the body towards the injury. However, chronic and progressive inflammation may lead to some chronic diseases. Due to the serious unwanted effects associated with available drugs, new and safe anti-inflammatory agents are still required. Therefore, the present study was designed to investigate the anti-inflammatory, analgesics, and antipyretic properties of a new compound (4-benzylpiperidine-1-carbodithioato-κ2S,S′)(1,4-bis-(diphenylphosphino)butane)palladium(II)chloride monohydrate (compound-1) in albino mice models. Compound-1 was characterized by elemental analysis, FT-IR, and multinuclear NMR spectroscopy. Initially, compound-1 was evaluated for cytotoxicity, anti-inflammatory, and analgesic activities by performing MTT assay, carrageenan-, histamine-, serotonin-, and CFA-induced paw edema, mechanical hyperalgesia, thermal hyperalgesia, and mechanical allodynia (0.1, 1, and 10 mg/kg, b.w). Antipyretic activity was evaluated in brewer’s yeast–induced model. The pro-inflammatory cytokines were measured by using commercially available ELISA kits. Additionally, nitrite production, antioxidant enzymes, H&E staining, muscle activity and motor coordination, and kidney and liver function tests were also determined. The results demonstrated that compound-1 significantly inhibited inflammation, pain, and febrile responses in all models at a dose of 10 mg/kg without effecting viability of cells in vitro at concentrations up to 100 μM. Similarly, the data clearly demonstrated significant reduction in the pro-inflammatory cytokines and nitrite production while enhancing antioxidant enzymes. Furthermore, pretreatment with compound-1 did not produce any prominent side effect on kidney, liver, stomach, and muscles. These findings suggest that compound-1 has potent anti-inflammatory-, pain-, and pyrexia-relieving properties. Hence, compound-1 might be a potential candidate for the therapeutic management of chronic inflammation and pain.


Heteroleptic palladium(II) complex Inflammation Pain Pyrexia Cytokines Antioxidant enzymes 


Author contributions

MN, AK, BS, and AA designed and performed research including behavioral and biochemical assays. SZK and ZR synthesized the compound. RU and Hussain Ali contributed new reagents and MTT assay. MN, SZ, and SK analyzed the data and drafted the manuscript. SK supervised the project. All authors read and approved the final manuscript.

Funding information

This work was supported by the Higher Education Commission (HEC), Pakistan under the SRGP funding (No. 357 SRGP/HEC/2014). This work is supported by the National Research Foundation of Korea (NRF) and Seoul National University, grant funded by the Korean Government (MSIP) (No. 2009-0083533).

Compliance with ethical standards

“Animal care guidelines of QAU” Islamabad were followed for the overall procedures involving animals. Bioethical Committee (Approval No. BEC-FBS-QAU 2017-59) of QAU University, Islamabad, approved the study. Maximum care was made sure to minimize harm to animals.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

210_2019_1645_MOESM1_ESM.doc (128 kb)
ESM 1 (DOC 128 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, Faculty of Biological SciencesQuaid-i-Azam UniversityIslamabadPakistan
  2. 2.Department of ChemistryQuaid-i-Azam UniversityIslamabadPakistan
  3. 3.Department of ChemistryUniversity of Science and TechnologyBannuPakistan
  4. 4.Department of PharmacyUniversity of PeshawarPeshawarPakistan

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