Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction

被引：1

作者：

Trung, Hieu Tran ^{[1
]}

Purnomo, Kartiko Arif ^{[2
]}

Yu, Szu-Yin ^{[2
,3
]}

Yang, Zih-Jie ^{[2
]}

Hu, Hao-Chun ^{[2
,4
,5
]}

Hwang, Tsong-Long ^{[5
,6
,7
,8
]}

Tuan, Nguyen Ngoc ^{[9
]}

Tu, Le Ngoc ^{[10
]}

Duc, Dau Xuan ^{[1
]}

Quang, Le Dang ^{[11
]}

Backlund, Anders ^{[12
]}

Thang, Tran Dinh ^{[9
]}

Chang, Fang-Rong ^{[2
,13
,14
]}

机构：

[1] Vinh Univ, Dept Chem, Vinh City 462030, Vietnam

[2] Kaohsiung Med Univ, Grad Inst Nat Prod, Coll Pharm, Kaohsiung 807378, Taiwan

[3] Univ Szeged, Inst Pharmacognosy, H-6720 Szeged, Hungary

[4] Univ Szeged, Inst Pharmaceut Chem, H-6720 Szeged, Hungary

[5] Chang Gung Univ, Grad Inst Nat Prod, Sch Tradit Chinese Med, Coll Med, Taoyuan 33302, Taiwan

[6] Chang Gung Univ Sci & Technol, Res Ctr Chinese Herbal Med, Res Ctr Food & Cosmet Safety, Taoyuan 333324, Taiwan

[7] Chang Gung Univ Sci & Technol, Grad Inst Hlth Ind Technol, Coll Human Ecol, Taoyuan 333324, Taiwan

[8] Chang Gung Mem Hosp, Dept Anesthesiol, Taoyuan 333423, Taiwan

[9] Ind Univ Ho Chi Minh City, Inst Biotechnol & Food Technol, Ho Chi Minh City 727000, Vietnam

[10] Ho Chi Minh City Univ Educ, Fac Chem, Ho Chi Minh City 749000, Vietnam

[11] Vietnam Acad Sci & Technol VAST, Inst Trop Technol, Hanoi 122000, Vietnam

[12] Uppsala Univ, Dept Pharmaceut Biosci, Res Grp Pharmacognosy, S-75124 Uppsala, Sweden

[13] Kaohsiung Med Univ, Drug Dev & Value Creat Res Ctr, Kaohsiung 807378, Taiwan

[14] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 807378, Taiwan

来源：

ACS OMEGA | 2023年 / 8卷 / 40期

关键词：

MOLECULAR DOCKING; HUMAN NEUTROPHILS; CLASSIFICATION; CONSTITUENTS; DERIVATIVES; INHIBITORS; MELANIN;

D O I：

10.1021/acsomega.3c04657

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Two new rearranged 2,3-seco-tirucallane triterpenoids, meliadubins A (<bold>1</bold>) and B (<bold>2</bold>), along with four known compounds, <bold>3</bold>-<bold>6</bold>, were isolated from the barks of Melia dubia Cav. Compound <bold>2</bold> exhibited a significant inflammatory inhibition effect toward superoxide anion generation in human neutrophils (EC50 at 5.54 +/- 0.36 mu M). It bound to active sites of a human inducible nitric oxide synthase (3E7G) through interactions with the residues of GLU377 and PRO350, which may benefit in reducing the neutrophilic inflammation effect. The ChemGPS-NP interpretation combined with bioactivity assay and in silico prediction results suggested <bold>2</bold> to be an agent for targeting iNOS with different mechanisms as compared to a selected set of current approved drugs. Moreover, compounds <bold>1</bold> and <bold>2</bold> showed remarkable inhibition against the rice pathogenic fungus Magnaporthe oryzae in a dose-dependent manner with IC50 values of 137.20 +/- 9.55 and 182.50 +/- 18.27 mu M, respectively. Both <bold>1</bold> and <bold>2</bold> displayed interactions with the residue of TYR223, a key active site of trihydroxynaphthalene reductase (1YBV). The interpretation of <bold>1</bold> and <bold>2</bold> in the ChemGPS-NP physical-chemical property space indicated that both compounds are quite different compared to all members of a selected set of reference compounds. In light of demonstrated biological activity and in silico prediction experiments, both compounds possibly exhibited activity against phytopathogenic fungi via a novel mode of action.

引用

页码：37116 / 37127

页数：12