Synthesis and evaluation of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-one derivatives as vasorelaxing agents

Sarita Singh; Karishma Agarwal; Hina Iqbal; Pankaj Yadav; Deepika Yadav; Debabrata Chanda; Sudeep Tandon; Feroz Khan; Anil Kumar Gupta; Atul Gupta

doi:10.1016/j.bmcl.2019.126759

Synthesis and evaluation of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-one derivatives as vasorelaxing agents

Bioorg Med Chem Lett. 2020 Jan 1;30(1):126759. doi: 10.1016/j.bmcl.2019.126759. Epub 2019 Oct 28.

Authors

Affiliations

¹ Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India.
² Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
³ Plant Biology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
⁴ Process Chemistry and Technology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
⁵ Genetic and Plant Breeding Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India.
⁶ Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India. Electronic address: atisky2001@yahoo.co.in.

PMID: 31711783
DOI: 10.1016/j.bmcl.2019.126759

Abstract

A series of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-ones (chromeno-coumarin hybrids) was synthesized from scopoletin (11) as vasorelaxing agents. The synthesized compounds 21a-f, 22, 23a-e and scopoletin (11) were evaluated for vasorelaxation in endothelium intact rat main mesenteric artery (MMA). Compounds 11, 21a, 21c-f and 22 showed significant vasorelaxation in precontracted MMA within the range of EC₅₀ value 1.58-5.02 µM. These derivatives presented 29.40-70.89 fold increased sensitivity for experimental tissue compared to scopoletin (11), the parent molecule. Among others, 22 was found to be the most active compound which had EC₅₀ 1.58 µM with 70.89 fold increased sensitivity. The mechanistic evaluation of 22 showed that it exerted vasorelaxation through Ca²⁺-activated K⁺ (BKca) channel and the effect was endothelium-independent.

Keywords: 8, 8-Dimethyl-8H-pyrano[2, 3-f]chromen-2-one; Chromeno-coumarin; Coumarin; Scopoletin; Vascular dysfunction; Vasorelaxation.

Publication types

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

MeSH terms

Drug Discovery / methods*
Humans
Structure-Activity Relationship
Vasodilation / drug effects*