N-Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents
Issued Date
2023-02-01
Resource Type
eISSN
14203049
Scopus ID
2-s2.0-85147893687
Pubmed ID
36770770
Journal Title
Molecules
Volume
28
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecules Vol.28 No.3 (2023)
Suggested Citation
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. N-Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents. Molecules Vol.28 No.3 (2023). doi:10.3390/molecules28031104 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/81665
Title
N-Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents
Other Contributor(s)
Abstract
New N-containing xanthone analogs of α-mangostin were synthesized via one-pot Smiles rearrangement. Using cesium carbonate in the presence of 2-chloroacetamide and catalytic potassium iodide, α-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 α-mangostin and analogs 2–4 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 brucei rhodesiense at a potency threefold stronger than that of α-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–RIMP2/PCM) indicated the improved binding interaction of 2 in the 3CLpro active site regarding an additional ether moiety. Thus, the series of N-containing α-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.