Computational simulations of identified marine-derived natural bioactive compounds as potential inhibitors of oral cancer

• Published in: Future science OA 2022-03, Vol.8 (3), p.FSO782-FSO782
• Main Authors: Natarajan, Prabhu Manickam, Umapathy, Vidhya Rekha, Murali, Anita, Swamikannu, Bhuminathan
• Format: Article
• Language: English
• Subjects: ADME; Akt1; Akt2; bioactive compounds; lipinski rule of five; marine algae; molecular docking; oral squamous cell carcinoma; PyRx; virtual screening
• ISSN: 2056-5623; 2056-5623
• DOI: 10.2144/fsoa-2021-0148

Oral squamous cell carcinoma is characterized by the upregulation of RAC-alpha serine/threonine-protein kinase (Akt1) and RAC-beta serine/threonine-protein kinase (Akt2). In this work, Akt1 and Akt2 were inhibited using a cocktail of 20 marine algae chemicals. From the PyRx Virtual Screening Tool, dieckol, 6,6′-bieckol, siphonaxanthin and sargachromanol E were chosen as the best four compounds for Akt1 based on the scoring. Similarly, dieckol, 6,6′-bieckol, dioxinodehydroeckol and caulerpenyne were chosen as Akt2 inhibitors. Additionally, the results of the Lipinski rule of five indicated that some of the selected compounds, such as dieckol, 6,6′-bieckol and siphonaxanthin, violated some Lipinski rules, but they demonstrated excellent binding in terms of scoring. Thus, this study demonstrates that the identified lead compounds may act against Akt1 and Akt2 in oral cancer. High-level expression of RAC-alpha serine/threonine-protein kinase (Akt1) and RAC-beta serine/threonine-protein kinase (Akt2) is responsible for oral cancer. Control of the expression of these target proteins will be used to control oral cancer. Marine algae are one of the best sources of anticancer compounds. Hence, 20 marine compounds were selected and their activities against Akt1 and Akt2 proteins were checked by using virtual screening techniques. The results of this screening rank the 20 compounds based on the binding score. The best four compounds for each target protein (Akt1: dieckol, 6,6′-bieckol, siphonaxanthin and sargachromanol E; Akt2: dieckol, 6,6′-bieckol, dioxinodehydroeckol and caulerpenyne) were selected. Expect for a few compounds most of the compounds satisfied the drug likeness quality. So dieckol,6,6'-bieckol,dioxinodehydroeckol and caulerpenyne, siphonaxanthin and sargachromanol E. may be a potential lead to further drug development for oral cancer.