Some metabolic enzyme inhibitors can be used as Multi-target-Directed-Ligands (MTDL) in Medicinal chemistry therefore, synthesis and determination of alternative inhibitors are essential. In this study, novel bisnapthoquinone derivatives (5a-o) were synthesized through a multi-component cascade reaction of two molecules of 2-hydroxy-1,4-naphthoquinone with an aromatic aldehyde in basic media using triethylamine as a catalyst. This novel heterocyclic derivatives (5a-o) are applied to inhibit the carbonic anhydrase (hCA I and hCA II) isoform in low levels of nano molecules with Ki values exist between 4.62 +/- 1.01 to 70.45 +/- 9.03 nM for hCA I and for hCA II which is physiologically dominant Kis values are in the range of 5.61 +/- 1.04 to 73.26 +/- 10.25 nM. Further these novel derivatives (5a-o) efficiently inhibit AChE with Ki values in the range of 0.13 +/- 0.02 to 3.16 +/- 0.56 nM. The compounds are also applied for BChE with Ki values varying between 0.50 +/- 0.10 to 9.23 +/- 1.15 nM. For alpha-glycosidase, the most efficient Ki values of 5e and 5f are 76.14 +/- 9.60 and 95.27 +/- 12.55 nM respectively. Finally, molecular docking calculations against enzymes (acetylcholinesterase, butyrylcholinesterase, and the human carbonic anhydrase I and II) are compared using biological activities of heterocyclic derivatives. After these calculations, an ADME/T analysis is performed to study the future medicinal use of heterocyclic derivatives from lawsone.