Synthesis, docking studies, biological activity of carbon monoxide release molecules based on coumarin derivatives

Abstract

In the present work, we synthesized seven complexes. All complexes were identified by ESI-HRMS, 1H-NMR, 19F-NMR and 13C-NMR spectroscopies. The synthesized complexes were tested for their anticancer activities in vitro against three different human cell lines, including breast MDAMB231, cervical Hela, liver HepG2. IC50 values of complexes 1-7 were 34.98–667.35 µM. Complex 5 revealed higher sensitivity towards MDAMB231 cells with IC50 values 34.98 μM in comparison to 5-FU as positive control. Moreover, complex 5 caused a decrease of mitochondrial membrane potential and effectively induced ROS production against MDAMB231 cells. Western blot analysis showed that complex 5 could up-regulate the expression of Bax protein and down-regulate the expression of Bcl-2, activate Caspase-3, slightly down-regulate the expression of HO-1. The docking studies showed that complex 5 could be interacted with Bcl-2 protein through hydrophobic interactions, hydrogen bonds and salt bridges to enhance the binding affinity. All the analyzed coumarins obeyed the Lipinski’s rule of five for orally administered drugs. Based on the aforementioned results, it suggests that the complex induced apoptosis cell via mitochondria pathways. Collectively, complex 5 could be considered as a promising hit for new anti-breast cancer agents. Carbonyl cobalt CORMs, as potential anticancer therapeutic agents, provided a new idea for the development of metal anticancer drugs.

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

“…Considering the scientific evidence and proven relevance of coumarin derivatives as modulators of the Nrf2 signaling pathway to increase endogenous antioxidant defense and promote several pharmacological properties, several studies have been performed to design and synthesize new coumarin derivatives able to activate Nrf2 signaling and its antioxidant response, including oximes bearing coumarin derivatives [165], chalcone-coumarin hybrid compounds [166], coumarin-derived imino sulfonates [167], carbon monoxide release coumarin complexes [168], and coumarin-containing hybrids [9][10][11][12]. Coumarins have special physicochemical properties, such as π-π conjugation, low molecular weight, simple chemical structure, high bioavailability, and solubility, rich in electrons and charge properties, which could bind to many targeted proteins to produce a wide range of biological activities [6,7,168]. Moreover, coumarin derivatives have low toxicity and high versatility for synthetic transformation into a variety of functionalized derivatives, ensuring them a prominent role as lead compounds in drug design and development [6,7].…”

“…Based on other coumarin derivative's chemical structures, structure-activity relationship analysis demonstrated that chemical modification at C-6, C-7, and C-8 as well as the presence of an α,β-unsaturated carbonyl group or free hydroxyl at C-8 increases antiinflammatory activity, including intestinal anti-inflammatory properties when compared with no substituted coumarins [84,168,171].…”

Coumarin-transition metal complexes with biological activity: current trends and perspectives

“…Liu and coworkers synthesized seven complexes, incorporating coumarin ligands and carbonyl cobalt with the aim of producing potential anticancer agents with the ability to release carbon monoxide ( Liu et al, 2022 ). Antiproliferative activity of the novel compounds was tested against Hep2G, HeLa, and MDA-MB-231 tumor cell lines (MTT assay, 10 μM–150 μM concentrations, 24 h incubation, 5-fluorouracil (5-FU) as a positive control).…”