Vol.:(0123456789) 1 3 Infammopharmacology https://doi.org/10.1007/s10787-018-0516-7 ORIGINAL ARTICLE Molecular docking and pharmacological/toxicological assessment of a new compound designed from celecoxib and paracetamol by molecular hybridization Daiany P. B. da Silva 1  · Iziara F. Florentino 1  · Dayane M. da Silva 1  · Roberta C. Lino 1  · Carina S. Cardoso 1  · Lorrane K. S. Moreira 1  · Géssica A. Vasconcelos 2  · Daniela C. Vinhal 3  · Anna C. D. Cardoso 4  · Bianca Villavicencio 5  · Hugo Verli 5  · Boniek G. Vaz 2  · Luciano M. Lião 2  · Luiz C. da Cunha 3  · Ricardo Menegatti 4  · Elson A. Costa 1 Received: 3 April 2018 / Accepted: 9 July 2018 © Springer Nature Switzerland AG 2018 Abstract Nonsteroidal anti-infammatory drugs are commonly used worldwide; however, they have several adverse efects, evidencing the need for the development of new, more efective and safe anti-infammatory and analgesic drugs. This research aimed to design, synthesize and carry out a pharmacological/toxicological investigation of LQFM-102, which was designed from celecoxib and paracetamol by molecular hybridization. To evaluate the analgesic efect of this compound, we performed formalin-induced pain, hot plate and tail fick tests. The anti-infammatory efect of LQFM-102 was evaluated in carrageenan- induced paw oedema and pleurisy tests. The biochemical markers indicative of toxicity—AST, ALT, GSH, urea and creati- nine—as well as the index of gastric lesion after prolonged administration of LQFM-102 were also analyzed. In addition, the interaction of LQFM-102 with COX enzymes was evaluated by molecular docking. In all experimental protocols, celecoxib or paracetamol was used as a positive control at equimolar doses to LQFM-102. LQFM-102 reduced the pain induced by formalin in both phases of the test. However, this compound did not increase the latency to thermal stimuli in the hot plate and tail fick tests, suggesting an involvement of peripheral mechanisms in this efect. Furthermore, LQFM-102 reduced paw oedema, the number of polymorphonuclear cells, myeloperoxidase activity and TNF-α and IL-1β levels. Another interesting fnding was the absence of alterations in the markers of hepatic and renal toxicity or lesions of gastric mucosa. In molecular docking simulations, LQFM-102 interacted with the key residues for activity and potency of cyclooxygenase enzymes, sug- gesting an inhibition of the activity of these enzymes. Keywords Gastric toxicity · Hepatotoxicity · Cytokines · Celecoxib · Paracetamol · LQFM-102 Introduction Despite the notorious adverse efects mainly related to gas- trointestinal tract and renal dysfunction, the nonsteroidal anti-infammatory drugs (NSAIDs) constitute a class of medications most commonly used worldwide (Sostres Inflammopharmacology Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10787-018-0516-7) contains supplementary material, which is available to authorized users. * Elson A. Costa xico@ufg.br 1 Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Campus Samambaia - ICB 2 - Sala 216, CP 131, Goiânia, GO CEP 74001-970, Brazil 2 Chemistry Institute, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil 3 Nucleus of Studies and Research Toxicopharmacological, Federal University of Goiás, Goiânia, GO, Brazil 4 Laboratory of Medicinal Pharmaceutical Chemistry, Faculty of Pharmacy, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil 5 Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil