• N-Containing ?-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic Antitrypanosomal and SARS-CoV-2 Main Protease Inhibitory Agents

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23/07/2024 by   

Metadata

Document Title

N-Containing ?-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic Antitrypanosomal and SARS-CoV-2 Main Protease Inhibitory Agents

Author

Pyae N.Y.L. Maiuthed A. Phongsopitanun W. Ouengwanarat B. Sukma W. Srimongkolpithak N. Pengon J. Rattanajak R. Kamchonwongpaisan S. Ei Z.Z. Chunhacha P. Wilasluck P. Deetanya P. Wangkanont K. Hengphasatporn K. Shigeta Y. Rungrotmongkol T. Chamni S.

Affiliations

Pharmaceutical Sciences and Technology Program Faculty of Pharmaceutical Sciences Chulalongkorn University Bangkok 10330 Thailand; Department of Pharmacognosy and Pharmaceutical Botany Faculty of Pharmaceutical Sciences Chulalongkorn University Bangkok 10330 Thailand; Natural Products and Nanoparticles Research Unit (NP2) Chulalongkorn University Bangkok 10330 Thailand; Department of Pharmacology Faculty of Pharmacy Mahidol University Bangkok 10400 Thailand; Centre of Biopharmaceutical Science for Healthy Ageing Faculty of Pharmacy Mahidol University Bangkok 10400 Thailand; Department of Biochemistry and Microbiology Faculty of Pharmaceutical Sciences Chulalongkorn University Bangkok 10330 Thailand; National Center for Genetic Engineering and Biotechnology (BIOTEC) National Science and Technology Development Agency Pathum Thani 12120 Thailand; Center of Excellence for Molecular Biology and Genomics of Shrimp Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand; Center of Excellence for Molecular Crop Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand; Center for Computational Sciences University of Tsukuba 1-1-1 Tennodai Ibaraki Tsukuba 305-8577 Japan; Center of Excellence in Biocatalyst and Sustainable Biotechnology Department of Biochemistry Faculty of Science Chulalongkorn University Bangkok 10330 Thailand; Program in Bioinformatics and Computational Biology Graduate School Chulalongkorn University Bangkok 10330 Thailand

Type

Article

Source Title

Molecules

ISSN

14203049

Year

2023

Volume

28

Issue

3

Open Access

All Open Access Gold Green

Publisher

MDPI

DOI

10.3390/molecules28031104

Abstract

New N-containing xanthone analogs of ?-mangostin were synthesized via one-pot Smiles rearrangement. Using cesium carbonate in the presence of 2-chloroacetamide and catalytic potassium iodide ?-mangostin (1) was subsequently transformed in three steps to provide ether 2 amide 3 and amine 4 in good yields at an optimum ratio of 1:3:3 respectively. The evaluation of the biological activities of ?-mangostin and analogs 2�was described. Amine 4 showed promising cytotoxicity against the non-small-cell lung cancer H460 cell line fourfold more potent than that of cisplatin. Both compounds 3 and 4 possessed antitrypanosomal properties against Trypanosoma燽rucei rhodesiense at a potency threefold stronger than that of ?-mangostin. Furthermore ether 2 gave potent SARS-CoV-2 main protease inhibition by suppressing 3-chymotrypsinlike protease (3CLpro) activity approximately threefold better than that of 1. Fragment molecular orbital method (FMO朢IMP2/PCM) indicated the improved binding interaction of 2 in the 3CLpro active site regarding an additional ether moiety. Thus the series of N-containing ?-mangostin analogs prospectively enhance druglike properties based on isosteric replacement and would be further studied as potential biotically active chemical entries particularly for anti-lung-cancer antitrypanosomal and anti-SARS-CoV-2 main protease applications. ? 2023 by the authors.

Industrial Classification

Health Care and Social Assistance

Knowledge Taxonomy Level 1

Biological Sciences

Knowledge Taxonomy Level 2

Pharmacology

Knowledge Taxonomy Level 3

Pharmacology and pharmacy

License

CC BY

Rights

Authors

Publication Source

Scopus

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