In vitro Photoprotective Evaluation and Development of Novel Nanoemulsion with Chromone Derivative

Amanda S Antunes ,Thiago Cazati,Gabriela M Diogo ,Jason G Taylor ,Ana Paula Martins Gouveia ,Paula Melo De Abreu Vieira ,Orlando David Henrique Dos Santos ,Ricardo Gonçalves Penido ,Tatiane Roquete Amparo ,Lucas Resende Dutra Sousa ,Fernanda Barçante Perasoli ,Viviane Martins Rebello Dos Santos

doi:10.21577/0103-5053.20210072

Abstract

Chromone derivatives exhibiting high absorbance values in the UVA/UVB region were synthesized, and their photoprotective properties were evaluated. Chromones were prepared according to known literature procedures and characterized by high resolution mass spectrometry, infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. The in vitro solar protection factor (SPF) was determined by the Mansur method and cytotoxicity was evaluated using the sulforhodamine B assay. Two of the chromones synthesized demonstrated suitable SPF values and displayed no cytotoxic effect towards MRC-5 human fibroblasts at the tested concentrations, indicating great potential for future in vivo assays and clinical trials. Finally, the lead compound was incorporated into a nanoemulsion. Nanoemulsions showed high droplet size homogeneity and excellent stability. Chromones bearing methoxy substituents were found to be the most promising compounds with ideal photoprotective properties desirable for utilization and incorporation in sunscreen formulations.

Highlights

Exposure to sun light and its UV radiation[1,2] is a contributing factor to developing cutaneous malignant melanoma which is one of the fastest growing types of cancer cases.[1]
Esterification of 2-hydroxyacetophenone with benzoyl chlorides initially yielded intermediates 1a-1c, which were subjected to a Baker-Venkataraman rearrangement in pyridine and potassium hydroxide to afford the expected 1,3-diketones 2a-2c (Scheme 1)
Products 3a-3c were characterized by high resolution mass spectrometry, Fourier transform infrared (FTIR) and 1H and 13C nuclear magnetic resonance spectroscopy

Summary

Introduction

Exposure to sun light and its UV radiation[1,2] is a contributing factor to developing cutaneous malignant melanoma which is one of the fastest growing types of cancer cases.[1]. The reactants were stirred for approximately 15 min at 25 °C After this time, 1 M HCl (60 mL) was added followed by crushed ice. the solid was filtered and the precipitate was washed with methanol and water (1:1). 3-Benzoyl-2-methyl-4H-chromen-4-one (3a) Product yield 16.6%; mp 118-119 °C; UV-Vis (methanol) λ / nm 365; IR (KBr) ν / cm-1 3000, 1700, 1650, 1500, 1450; 1H NMR (400 MHz, CDCl3) d 2.38 (s, 3H, H12), 7.39-7.61 (m, 3H), 7.68 (t, 2H, J 8.4 Hz), 7.71 (t, 1H, J 8.4 Hz), 7.90 (d, 2H, J 7.6 Hz), 8.16 (d, 1H, J 7.9 Hz); 13C NMR (100 MHz, CDCl3) d 29.7, 117.9, 123.1, 125.5, 128.7, 130.0, 133.8, 136.9, 155.9, 165.4, 175.9, 193.9, according to Figures S1 and S2 (SI section); HRMS electrospray ionization time-of-flight (ESI-TOF) m/z, calcd. All statistical analysis was made using Graph Pad Prism 5.0 software.[30]

Results and Discussion

Evaluation of photostability

Conclusions