Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae

Sanjay Kumar; Amol Dilip Pagar; Furkan Ahmad; Vagish Dwibedi; Aabid Wani; Prasad V Bharatam; Manmohan Chhibber; Sanjai Saxena; Inder Pal Singh

doi:10.1016/j.bioorg.2018.12.008

Xanthine oxidase inhibitors from an endophytic fungus Lasiodiplodia pseudotheobromae

Bioorg Chem. 2019 Jun:87:851-856. doi: 10.1016/j.bioorg.2018.12.008. Epub 2018 Dec 10.

Authors

Sanjay Kumar¹, Amol Dilip Pagar¹, Furkan Ahmad¹, Vagish Dwibedi², Aabid Wani³, Prasad V Bharatam³, Manmohan Chhibber⁴, Sanjai Saxena⁵, Inder Pal Singh⁶

Affiliations

¹ Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar 160 062, Punjab, India.
² Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab 147004, India.
³ Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar 160 062, Punjab, India.
⁴ School of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala, Punjab 147004, India.
⁵ Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab 147004, India. Electronic address: ssaxena@thapar.edu.
⁶ Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar 160 062, Punjab, India. Electronic address: ipsingh@niper.ac.in.

PMID: 30545575
DOI: 10.1016/j.bioorg.2018.12.008

Abstract

Two new compounds, lasdiplactone (1) and lasdiploic acid (2) and one known compound 3 were isolated from the chloroform extract of cell free filtrate of the endophytic fungus Lasiosdiplodia pseudotheobromae. The structures of new compounds were determined by interplay of spectral techniques (IR, mass, ¹H NMR, ¹³C NMR, DEPT, and 2D NMR). The absolute configuration at C-4 position of 1 was established as S using a process similar to modified Mosher's method. The absolute configuration of 2 was established by comparing its ECD spectrum with the calculated ECD spectra of all possible isomers. In the in vitro XO inhibition assay, the highest inhibition was exhibited by 3 with an IC₅₀ of 0.38 ± 0.13 μg/ml, followed by 2 with an IC₅₀ of 0.41 ± 0.1 μg/ml and the least in 1. The oxidized form of 1 also showed high XO inhibition with IC₅₀ of 0.35 ± 0.13 μg/ml.

Keywords: Absolute configuration; Endophytic fungus; Lasdiplactone; Lasdiploic acid; Lasiodiplodia pseudotheobromae; Xanthine oxidase inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ascomycota / chemistry*
Dose-Response Relationship, Drug
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / pharmacology*
Humans
Molecular Structure
Structure-Activity Relationship
Xanthine Oxidase / antagonists & inhibitors*
Xanthine Oxidase / metabolism

Substances

Enzyme Inhibitors
Xanthine Oxidase