Synthesis of nonsteroidal anti-inflammatory drug (NSAID) 2,4,5-trimethoxybenzaldehyde from Indonesian calamus oil and its in silico pharmacokinetic study

Abstract

There is a race to search for nonsteroidal anti-inflammatory painkillers due to the escalating cases of the life-threatening COVID-19 pandemic. Those current nonsteroidal anti-inflammatory drugs (NSAIDs) used as an inflammation adjunct treatment on COVID-19 patients, including paracetamol, ibuprofen, and celecoxib, are still under dispute offering emergency development of a new potent NSAID. Meanwhile, a well-known COX-2 selective anti-inflammation 2,4,5-trimethoxybenzaldehyde (TMBA) has not been developed further in terms of its synthetic methodology and its pharmacokinetic studies. Herein, the synthesis of 2,4,5-TMBA from Indonesia sweet flag ( Acorus calamus) and its pharmacokinetic properties was studied through in silico calculation. A typical Asian tetraploid calamus oil was yielded ( 90% pure) after reduced pressure distillation of the crude Indonesian sweet flag oil. Submission of that oil into a very cheap DIY ozone machine produced 95% of pure 2,4,5-TMBA just in 10 min ozonised. The in silico adsorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction using the free access ADMETlab 2.0 web server strongly recommended 2,4,5-TMBA to be an orally administered NSAID candidate.