Identification Of Novel Inhibitors Against Cyclin-Dependent Kinase From Phytocompounds Of Citrus Sinensis Peel Extract By In Silico Approach

Abstract

Sweet orange, biologically known as Citrus sinensis, is a citrus fruit with a significant medicinal value. In this study, the bioactive compounds of C. sinensis in ethanolic peel extract were identified using gas chromatography-mass spectrometry (GC-MS) and their inhibitory effect on the activity of Cyclin-dependent kinase (CDK), which controls apoptosis, was tested. 12 phytocompounds were isolated from C. sinensis' ethanolic peel extract using gas chromatography-mass spectrometry (GC-MS). The SwissADME web program was used to determine the pharmacokinetics and drug-likeness of every compound. The findings were in agreement with Lipinski Rule of Five, the data reflected desirable oral bioavailability and drug-like properties. Additionally, PyRx virtual screening tool was used to dock molecules to measure CDK binding affinity. Discovery Studio Visualiser was used to carry out interaction analysis. Numerous phytocompounds showed significant affinity for the CDK active site in docking tests. The compounds with the highest docking scores were phthalic acid (-6.3 kcal/mol), 2-methoxy-4-vinyl phenol (-5.3), and 4-vinyl phenol (-6). The findings demonstrate that Citrus sinensis peel bioactive components suppress CDK, suggeststing their possible therapeutic implications in various diseases particularly in cancer. Nevertheless, additional in vitro and in vivo research is required to validate the therapeutic effectiveness of the compounds.