2. Academic Validation
  3. 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

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

  • ACS Omega. 2023 Sep 27;8(40):37116-37127. doi: 10.1021/acsomega.3c04657.
Hieu Tran Trung 1,  Kartiko Arif Purnomo 2,  Szu-Yin Yu 2 3,  Zih-Jie Yang 2,  Hao-Chun Hu 4 2 5,  Tsong-Long Hwang 4 6 7,  Nguyen Ngoc Tuan 8,  Le Ngoc Tu 9,  Dau Xuan Duc 1,  Le Dang Quang 10,  Anders Backlund 11,  Tran Dinh Thang 8,  Fang-Rong Chang 2 12 13
Affiliations

Affiliations

  • 1 Department of Chemistry, Vinh University, Vinh City 462030, Viet Nam.
  • 2 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
  • 3 Institute of Pharmacognosy, University of Szeged, Szeged 6720, Hungary.
  • 4 Graduate Institute of Natural Products, School of Traditional Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan.
  • 5 Institute of Pharmaceutical Chemistry, University of Szeged, Szeged 6720, Hungary.
  • 6 Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333324, Taiwan.
  • 7 Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan.
  • 8 Institute of Biotechnology and Food Technology, Industrial University of Ho Chi Minh City, Ho Chi Minh City 727000, Viet Nam.
  • 9 Faculty of Chemistry, Ho Chi Minh City University of Education, Ho Chi Minh City 749000, Viet Nam.
  • 10 Institute for Tropical Technology, Vietnam Academy of Science and Technology (VAST), Hanoi 122000, Viet Nam.
  • 11 Research Group Pharmacognosy, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala S-75124, Sweden.
  • 12 Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
  • 13 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
PMID: 37841162 DOI: 10.1021/acsomega.3c04657
Abstract

Two new rearranged 2,3-seco-tirucallane triterpenoids, meliadubins A (1) and B (2), along with four known compounds, 3-6, were isolated from the barks of Melia dubia Cav. Compound 2 exhibited a significant inflammatory inhibition effect toward superoxide anion generation in human neutrophils (EC50 at 5.54 ± 0.36 μM). 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 2 to be an agent for targeting iNOS with different mechanisms as compared to a selected set of current approved drugs. Moreover, compounds 1 and 2 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 μM, respectively. Both 1 and 2 displayed interactions with the residue of TYR223, a key active site of trihydroxynaphthalene reductase (1YBV). The interpretation of 1 and 2 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.

Figures
Products