2'-Hydroxy-4',5'-dimethoxyacetophenone Exhibit Collagenase, Aldose Reductase Inhibition, and Anticancer Activity Against Human Leukemic Cells: An In Vitro, and In Silico Study.

Abstract

Diabetes is a serious growing concern that affects many parts of the body including the skin due to high sugar levels. Moreover, diabetic patients are at risk of developing cancer and are prone to a higher risk of hematological malignancies. In the present study, the inhibitory effect of 2'-Hydroxy-4',5'-dimethoxyacetophenone was investigated on aldose reductase and collagenase enzymes, along with docking and ADMET analysis. MTT assay was also conducted to investigate the anti-leukemic effect of 2'-Hydroxy-4',5'-dimethoxyacetophenone on human acute leukemia cells (32D-FLT3-ITD, Human HL-60/vcr, MOLT-3, and TALL-104 cell lines) and DPPH assay for establishing activity against oxidative stress. The 2'-Hydroxy-4',5'-dimethoxyacetophenone showed potent inhibition of both the above tested enzymes with numerous strong interactions with the key catalytic residues in the active site of the enzymes. The MTT assay showed strong anti-cancer activity against entire tested human acute leukemia cells and was found non-toxic to normal (HUVEC) at the tested concentration. In DPPH free radical scavenging assay, 2'-Hydroxy-4',5'-dimethoxyacetophenone showed strong inhibitory activity with IC50 of 157µg/mL, which found comparable to the standard BHT. Our study demonstrated prominent pharmacological benefit of 2'-Hydroxy-4',5'-dimethoxyacetophenone, against various leukemic cell lines, aldose reductase and collagenase enzymes, and free radical scavenging activity.