In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma

Abstract

Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.

Synthesis and molecular docking studies of novel tricyclic and angular tetracyclic benzothiadiazines via sp3‐C‐Hactivation as potential colon cancer inhibitors

“…The presence of six strong hydrogen bonds with tankyrase‐2 transferase (Figure 21) could be one of the major reasons for its selection as an anticancer drug. Uniquely, K9 and S7 also exhibit hydrogen binding interactions (Figures 18, 21), and despite being fewer, they have higher binding energy than capecitabine, which could be attributed to the geometry of the synthesized compound in the active binding pockets of the receptor [53].…”

Complement System Inhibitory Drugs in a Zebrafish (Danio rerio) Model: Computational Modeling

“…When transposed to an in vivo toxicity study, clear evidence was found that the molecular interaction effect observed in the virtual environment was somewhat similar to that of the biological model [ 86 ]. Furthermore, the transposition of in silico virtual screening of anticancer drugs using the receptors caspase-3, Bcl-2 and TRAF2 and the interaction proteins kinase and cyclin-dependent kinase 2 (CDK2) to an in vitro trial was validated through the in vitro anticancer activity against HCT-116 and the cell line HeLa [ 87 ]. In addition, results from molecular docking studies were crucial for validating the interactions of twenty phytocompounds with high binding affinity for the target receptors AChE, COX2 and MMP8, which are involved in the physiopathology of Alzheimer’s disease.…”

Marine-derived sea urchin compounds as potential anti-cancer drug candidate against colorectal cancer: In silico and in vitro studies

“…ADME property analysis proved that the selected four compounds have the ability to be used as drug candidates against the HCT116 cell line. The study of colorectal cancer found that the ADME result predicted the toxicity and pharmacokinetic properties of Emodin and Chrysophanol ( Ahmad et al, 2022 ). In our study, we selected four compounds that had no toxic substance for humans as drug candidates through the ProToxII software, where several studies reported the same result ( Banerjee et al, 2018 ).…”