Anti-Colon Cancer, Anti-HMG-CoA Reductase, Anti-Urease Activities, and Molecular Docking Studies of Some Natural Compounds

The creation of novel enzyme inhibitors and anti-cancer therapeutics has recently been one of medicinal chemistry's main objectives. Furthermore, the β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase and urease enzyme inhibition activities of these compounds were investigated. The obtained results revealed that Bavachalcone, with IC۵۰ value of ۱۳.۲۷±۱.۳۸ µM against HMG-CoA reductase, and Ladanein with IC۵۰ value of ۳.۰۸±۰.۲۵ µM against urease, were the most potent compounds against both assigned enzymes. It should be emphasized that all substances were more effective at inhibiting both enzymes than the common inhibitor tacrine. The chemical activities of bavachalcone, isobavachalcone, ladanein, and salvigenin against pancreatic HMG-COA reductase and urease were evaluated by conducting a molecular docking study. The anti-cancer activities of these compounds were investigated against colon cancer cells such as SNU-C۱, SW۴۸, RKO, COLO-۲۰۵, SW۱۴۱۷, and LS۴۱۱N. The chemical activities of bavachalcone, isobavachalcone, ladanein, and salvigenin against some of the expressed surface receptor proteins (CD۴۴, endothelin receptor, EGFR, CD۴۷, CXCR۴, and HER۲) in the mentioned cell lines were assessed using the molecular docking calculations. In the cancer part, all of the investigated molecules, exhibited the most potent growth inhibition in the six colon cancer cells, with an IC۵۰ value of ۵.۵۶–۲۰۰ µM, indicating that they are more powerful than ۵FU, which exhibited an IC۵۰ value of ۳۷.۳۶±۴.۶۹–۵۶.۰۶±۶.۸۲ µM except for Ladanein. The docking scores showed that these compounds have strong binding affinities to the enzymes and receptors. In addition, the compounds formed strong contacts with the proteins. Thus, these compounds could be potential inhibitors for enzymes and cancer cells.

کلیدواژه ها:

natural compounds ، HMG-COA reductase ، Urease ، Colon cancer ، Molecular modeling