학술논문
N -Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents.
Document Type
Article
Author
Pyae, Nan Yadanar Lin; Maiuthed, Arnatchai; Phongsopitanun, Wongsakorn; Ouengwanarat, Bongkot; Sukma, Warongrit; Srimongkolpithak, Nitipol; Pengon, Jutharat; Rattanajak, Roonglawan; Kamchonwongpaisan, Sumalee; Ei, Zin Zin; Chunhacha, Preedakorn; Wilasluck, Patcharin; Deetanya, Peerapon; Wangkanont, Kittikhun; Hengphasatporn, Kowit; Shigeta, Yasuteru; Rungrotmongkol, Thanyada; Chamni, Supakarn
Source
Subject
*MOLECULAR orbitals
*SARS-CoV-2
*NON-small-cell lung carcinoma
*GRANZYMES
*POTASSIUM iodide
*NUCLEOPHILIC substitution reactions
*CISPLATIN
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Language
ISSN
1420-3049
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. [ABSTRACT FROM AUTHOR]