Pulchranin A: First report of isolation from an endophytic fungus and its inhibitory activity on cyclin dependent kinases

Ashaimaa Y Moussa; Nada M Mostafa; Abdel Nasser B Singab

doi:10.1080/14786419.2019.1585846

Pulchranin A: First report of isolation from an endophytic fungus and its inhibitory activity on cyclin dependent kinases

Nat Prod Res. 2020 Oct;34(19):2715-2722. doi: 10.1080/14786419.2019.1585846. Epub 2019 Mar 19.

Authors

Ashaimaa Y Moussa¹, Nada M Mostafa¹, Abdel Nasser B Singab^{1

2}

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University , Cairo , Egypt.
² Center for Drug Discovery Research and Development, Ain Shams University , Cairo , Egypt.

PMID: 30887847
DOI: 10.1080/14786419.2019.1585846

Abstract

Fungal factories emerge as a promising source for the production of bioactive natural products. This study reports the isolation and structure elucidation of pulchranin A, for the first time, from an endophytic fungus (Aspergillus TRL1), which was cultured from Tabebuia rosea (Bignoniaceae) stems and identified by DNA ITS sequencing. Pulchranin A showed promising in-vitro cytotoxic effects against breast (MCF-7), liver (Hep-G2) and colorectal (HCT) cell lines, with IC₅₀ values of 63, 80 and 91 µg/mL, respectively. In addition, it inhibited three cyclin-dependent kinases (CDK1, CDK2 and CDK4) in MCF-7 cells with IC₅₀ values of 9.82, 15.6 and 2.7 µg/mL, respectively. Results were further supported by in-silico molecular docking of pulchranin A to CDK1, CDK2, and CDK4 crystal structures, where it demonstrated good interactions by H-bonding, hydrophobic and Pi-Pi interactions with different amino acid residues of these enzymes. Pulchranin A might be a potential CDK inhibitor in human breast cancer cells.[Figure: see text].

Keywords: Aspergillus; Tabebuia; cyclin-dependent kinase inhibitor; cytotoxic effect; molecular docking.

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Aspergillus / chemistry*
Aspergillus / genetics
Aspergillus / isolation & purification
Bignoniaceae / microbiology
CDC2 Protein Kinase / antagonists & inhibitors
CDC2 Protein Kinase / chemistry
CDC2 Protein Kinase / metabolism
Cyclin-Dependent Kinase 2 / antagonists & inhibitors
Cyclin-Dependent Kinase 2 / chemistry
Cyclin-Dependent Kinase 2 / metabolism
Cyclin-Dependent Kinase 4 / antagonists & inhibitors
Cyclin-Dependent Kinase 4 / chemistry
Cyclin-Dependent Kinase 4 / metabolism
Cyclin-Dependent Kinases / antagonists & inhibitors*
Cyclin-Dependent Kinases / metabolism
Endophytes / chemistry
Guanidines / chemistry*
Guanidines / pharmacology*
Hep G2 Cells
Humans
Hydrogen Bonding
MCF-7 Cells
Molecular Docking Simulation
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*

Substances

Antineoplastic Agents
Guanidines
Protein Kinase Inhibitors
pulchranin A
CDC2 Protein Kinase
CDK1 protein, human
CDK2 protein, human
CDK4 protein, human
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases