Discovery of pyridoindole derivatives as potential inhibitors for phosphodiesterase 5A: in silico and in vivo studies

Abstract

The aim of this work was to synthesise derivatives from identified plant based pyridoindole lead scaffold, and to assess phosphodiesterase 5A inhibitory potential by in silico and in vivo. Pyridoindole derivatives were synthesised by using six-stage reactor. In silico screening was carried out by grip-based docking methodology. In step-I, tryptophan as a starting material was reacted with different aldehydes and ketones to obtain 11 molecules. In step-II, obtained molecules were reacted with ethanol and benzyl alcohols to obtain D1 to D22 derivatives. In silico investigation resulted in best three molecules D12, D4 and D8 with promising BE score. Oral acute toxicity study of selected molecules resulted in LD50 value 500 mg/kg in rats. The result of in vivo antihypertensive study shown that molecule D12 was found to be the best antihypertensive lead molecule. This study could be a best platform to tailor novel biomolecules for inhibiting phosphodiesterase 5A enzyme in hypertension management.