Antikanser etkili 6-gingerol ve benzeri bileşiklerin olası ın silico hedeflerinin tahmini

Cancer still affects millions of people and causes death around the globe. Due to its prevalence, the discovery of novel anticancer drugs has always been a hot topic in pharmaceutical chemistry. Natural products provide a reliable source of bioactive substances and a rich resource for novel therapeutic leads. Also, the phyto-substances have fewer side effects, are relatively affordable, and offer a potent alternative. Hence, in our study, the 6-gingerol was focused on, as one of the polyphenols in ginger (Zingiber officinale Roscoe) characterized by a diversity of biological activities, specifically anti-cancer activity. Similar analogues of 6-gingerol were firstly screened by using similarity screening and then the putative biological targets of 6-gingerol and its similar compounds were investigated by using in silico target fishing servers. Their effect on the kinases as an anti-cancer target were specifically focused on. The docking study was performed for the 6-gingerol and its similars with the B-Raf proto-oncogene serine/threonine kinase (BRAF), Janus kinase (JAK1/2), extracellular signal-regulated kinase (ERK1(MAPK3)), and human p38 mitogen-activated kinase (p38γ) crystal structures. Computational studies revealed that vanylglycol, L-(+)-vanillylmandelic acid, dehydrozingerone, 2-methoxyestrone, methylvanillate, dihydroconiferyl aldehyde, pratensein, acetovanillone, acetosyringone, licochalcone B, isoferulic acid, curcumin PE, and coniferaldehyde can interact with at least one of these targets. Also, all these studied compounds satisfied Lipinski's rule of five. The computational approaches that were used for toxicity predictions revealed that none of the compounds have toxicity on cardiac and hepatic organs. Furthermore, these selected compounds have toxicities on one or more tumor cells. Eventually, the in silico target and toxicity predictions revealed that these similar molecules to 6-gingerol, are possible anticancer candidates that could be developed further within future lead optimization studies.