Work

Synthesis and Evaluation of 9-epi-Koshidacin B as Selective Inhibitor of Histone Deacetylase 1

Year: 2024

Type: article

Abstract: A concise synthetic route to an epimer of the recently isolated biologically active cyclic tetrapeptide koshidacin B has been developed, which featured a late-stage functionalization of a macrocyclic scaffold through a cross metathesis reaction. The synthetic 9- epi -koshidacin B showed marginal differences in spectroscopic behavior with that of the natural product but exhibited conformational preferences similar to those reported for analogous substrate chlamydocin. Moreover, it exhibited a useful level of selective inhibition of biologically relevant enzyme histone deacetylase 1 with an IC 50 value of 0.145 μM over two other isoforms. Docking studies indicate that the natural product as well as its 9-epimer binds very similarly to the active site of HDAC1 indicating little influence of the configuration of the C9-stereocenter.

Source: Journal of Natural Products

DOI: 10.1021/acs.jnatprod.4c00913

Authors: Rajat Ghosh, Sima Biswas, Angshuman Bagchi, Shital K. Chattopadhyay

Institution: University of Kalyani

Language: English

Topic: Histone Deacetylase Inhibitors Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: Department of Science and Technology, Ministry of Science and Technology, India

Award: G7081152180