Diacylphloroglucinol derivatives as antioxidant agents: green synthesis, optimisation, in vitro, and in silico evaluation

Abstract

Several derivatives of diacylphloroglucinol (3a–3c and 5a–5b) as an analogue of natural product compound 2,4-diacetylphloroglucinol 3a, were successfully synthesised in an excellent yield via a greener Friedel–Craft acylation using methanesulfonic acid (MSA) as a catalyst under an ultrasound-assisted condition. Operational simplicity, excellent yield, expedient metal-free synthesis, energy-efficient and mild reaction conditions are the outstanding advantages in this procedure. A scaled-up reaction also revealed the practical suitability of this newly developed procedure. The effects of several process variables on 3a were carefully accomplished using response surface methodology (RSM). Moreover, the green credentials of the present protocol have been assessed using several established green metrics and compared to relevant procedures. Along with the monomers, dimeric diacylphloroglucinols (6a–6e) were also synthesised and their in vitro antioxidant activity of these species were carried out. Furthermore, drug-likeness, density functional theory (DFT), and molecular docking studies were also established.

GRAPHICAL ABSTRACT

Keywords:

• Andraos algorithm
• diacylphloroglucinol
• Friedel-Crafts acylation
• greenness assessment
• molecular docking
• response surface methodology
• ultrasound- assisted

Disclosure statement

There are no conflicts to declare.

Additional information

Funding

This work was supported by the Hibah Pascasarjana 2019 under Grant number 516/UN27.21/PP/2019 and Hibah Pascasarjana 2020 under Grant number 452/UN27.21/PN/2020.