Synthesis, characterization, computational assay and anti-inflammatory activity of thiosemicarbazone derivatives: Highly potent and efficacious for COX inhibitors

• DOI: 10.1016/j.intimp.2023.111259
• Publication Date: 2023-11-22T04:08:16Z
• Authors: Kinza Saeed; Muhammad Rafiq; Muhammad Khalid; Ajaz Hussain; Farhan Siddique; Muhammad Hanif; Saghir Hussain; Khalid Mahmood; Nabeela Ameer; Muhammad Mahboob ...; Muhammad Ali Khan; Muhammad Yaqub; Mehreen Jabeen
• Keywords: Molecular Docking Simulation; Thiosemicarbazones; Inflammation; Structure-Activity Relationship; Sheep; Molecular Structure; Cyclooxygenase 2 Inhibitors; Anti-Inflammatory Agents; Animals; Humans; Edema; Carrageenan; 3. Good health

Multiple studies in the literature have demonstrated that synthetic compounds containing heterocyclic rings possess a reparative potential against acute and chronic inflammation. In the present study, two novel thiosemicarbazone derivatives based on l-ethyl-6-(thiophen-2-yl)indoline-2,3-dione with different phenyl substituted thiosemicarbazides were synthesized by condensation reaction and the structures of proposed target compounds (KP-2 and KP-5) were confirmed by UV-VIS, FTIR, 1H-NMR and 13C-NMR. In-vitro anti-inflammatory behavior of KP-2 and KP-5 was confirmed by bovine serum albumin (BSA) and ovine serum albumin (OSA) analysis. Acute and chronic anti-inflammatory potential of synthesized compounds were evaluated by using carrageenan and complete Freund's adjuvant (CFA) as inflammation-inducing agents, respectively. Inhibition of pro-inflammatory mediators and prevention of protein denaturation owing to synchronization of more electronegative flouro-groups substituted on phenyl rings along with heterocyclic indoline ring provides anti-inflammatory effects and are corroborated by radiological, histopathological analysis. Additional support was provided through density functional theory (DFT) and molecular docking. KP-5 exhibited excellent lead-likeness based on its physicochemical parameters, making it a viable drug candidate. The synthesized compounds also showed promising ADMET properties, enhancing their potential as therapeutic agents. These findings emphasize the pivotal role of new compounds for drug design and development.