Synthesis of newly functionalized 1,4-naphthoquinone derivatives and their effects on wound healing in alloxan-induced diabetic mice

• Published in: Chemico-biological interactions Vol. 291; pp. 55 - 64
• Main Authors: Cardoso, Silvia Helena, de Oliveira, Cleidijane Rodrigues, Guimarães, Ari Souza, Nascimento, Jadiely, de Oliveira dos Santos Carmo, Julianderson, de Souza Ferro, Jamylle Nunes, de Carvalho Correia, Ana Carolina, Barreto, Emiliano
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.08.2018
• Subjects: Diabetes; Naphthoquinone derivatives; Wound healing; Naphthoquinone derivatives; Wound healing; Diabetes
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2018.06.007

Naphthoquinone derivatives have various pharmacological properties. Here, we describe the synthesis of new 1,4-naphthoquinone derivatives inspired by lawsone and β-lapachone and their effects on both migration of fibroblasts in vitro and dermal wound healing in diabetic mice. NMR and FTIR spectroscopy aided characterization of chemical composition and demonstrated the molecular variations after the synthesis of four different derivatives, namely 2-bromo-1,4-naphthoquinone (termed derivative S3), 2-N-phenylamino-1,4-naphthoquinone (derivative S5), 2-N-isonicotinoyl-hydrazide-1,4-naphthoquinone (derivative S6), and 1-N-isonicotinoyl-hydrazone-[2-hydroxy-3-(3-methyl-2-butenyl)]-1,4-naphthoquinone (derivative S7). Our results indicate that derivatives S3, S5, S6 and S7 were non-toxic to the 3T3 fibroblast cell line. In scratch assays, derivatives S3 and S6, but not S5 or S7, stimulated the migration of fibroblasts. Compared with untreated diabetic mice, S3, S6 and S7 treatments accelerated wound closure. However, derivative S3 was optimal for the stimulation of epithelization, thereby increasing the number of keratinocyte layers and blood vessels, and reducing diffuse cellular infiltration, compared to derivatives S6 and S7. Our results suggest that novel 1,4-naphthoquinone derivatives promote fibroblast migration and accelerate wound closure under diabetic conditions. •1,4-Naphthoquinone derivatives were synthesized and characterized.•Synthesized 1,4-naphthoquinones promoted fibroblast migration in vitro.•1,4-Naphthoquinone derivatives improved the healing process in diabetic wounds by inhibiting the inflammation phase.