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

ABSTRACT: 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.

SUBMITTER: Natarajan PM

PROVIDER: S-EPMC8890117 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Natarajan Prabhu Manickam PM Umapathy Vidhya Rekha VR Murali Anita A Swamikannu Bhuminathan B

Future science OA 20220124 3

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 w ...[more]

PMID: 35251696

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Project description:BackgroundRecent reports have highlighted the significance of plant bioactive components in drug development targeting neurodegenerative disorders such as Alzheimer's disease (AD). Thus, the current study assessed antioxidant activity and enzyme inhibitory activity of the aqueous extract of Talinum triangulare leave (AETt) as well as molecular docking/simulation of the identified phytonutrients against human cholinesterase activities.MethodsIn vitro assays were carried out to assess the 2,2- azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) cation radicals and cholinesterase inhibitory activities of AETt using standard protocols. High performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was employed to identify compounds in AETt. Also, for computational analysis, identified bioactive compounds from AETt were docked using Schrodinger's GLIDE against human cholinesterase obtained from the protein data bank ( https://www.rcsb.org/ ).ResultsThe results revealed that AETt exhibited a significant concentration-dependent inhibition against ABTS cation radicals (IC50 = 308.26 ± 4.36 µg/ml) with butylated hydroxytoluene (BHT) as the reference. Similarly, AETt demonstrated a significant inhibition against acetylcholinesterase (AChE, IC50 = 326.49 ± 2.01 µg/ml) and butyrylcholinesterase (BChE, IC50 = 219.86 ± 4.13 µg/ml) activities with galanthamine as the control. Molecular docking and simulation analyses revealed rutin and quercetin as potential hits from AETt, having showed strong binding energies for both the AChE and BChE. In addition, these findings were substantiated by analyses, including radius of gyration, root mean square fluctuation, root mean square deviation, as well as mode similarity and principal component analyses.ConclusionOverall, this study offers valuable insights into the interactions and dynamics of protein-ligand complexes, offering a basis for further drug development targeting these proteins in AD.

Project description:Marine natural products (MNPs) have been an important and rich source for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein, we report bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: aniline 1, benzylamine 2, tertiary amine 3 and 4, and quaternary amine salt 5, along with three known compounds (6-8) were isolated from a crude extract and MeOH eluent marine extracts. The antibiotic activities of the compounds, and their isolation as natural products have not been reported before. Using tandem mass spectrometry (MS) analysis, potential structures of the bioactive fractions were assigned, leading to the hit validation of potential compounds through synthesis, and commercially available compounds. This method is a novel strategy to overcome insufficient quantities of pure material (NPs) for drug discovery and development which is a big challenge for pharmaceutical companies. The antibacterial screening of the marine extracts has shown several of the compounds exhibited potent in-vitro antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values between 15.6 to 62.5 microg mL-1. Herein, we also report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure-activity relationships (SAR) results demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity. Several commercially available compounds, which are structurally related to the discovered molecules, showed broad-spectrum antimicrobial activity against different test pathogens with a MIC range of 50 to 0.01 µM. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds have increased bioactivity.

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

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

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