Benzopyrylium salts as new anticancer, antibacterial, and antioxidant agents

Abstract

Benzopyrylium salts are an unexplored class of compounds and as a first, this study reports them as potential therapeutic agents. In this effort we pursue the synthesis and in vitro anticancer, antibacterial and antioxidant properties of some novel benzopyrylium salts. The benzopyrylium salts were synthesized and further characterized via UV-vis, IR, 1 H-NMR, 13 C-NMR and mass spectrometry. The benzopyrylium salts were tested in vitro for anticancer activity across NCI 60 cell line panel. PS-CP-4MO showed the best activity against the MDA-MB-435 cell line of melanoma cancer in terms of the least GI 50 (1.78 μM), TGI (3.47 μM) and LC 50 (6.77 μM) values and showed selectivity against melanoma, colon cancer and leukemia. Mechanistic studies indicate that this compound inhibits MCF-7 cancer cells by inducing apoptosis and abrogates colony formation and wound healing in the cancer cells. Antibacterial studies show that some of the benzopyrylium salts are active on S. aureus (ATCC 29213) and the best active compound PS-CP-5Cl has a MIC of 8 μg/mL. Antioxidant studies indicate that they have good free radical scavenging properties (PS-CP-5Cl showed activity 1.48 times ascorbic acid). Fulfillment of the Lipinski's parameters of the benzopyrylium salts in silico showed tremendous drug likeness as potential pharmacophore leads.

Combined Transcriptome and Metabolome Analysis Reveals That the Potent Antifungal Pyrylium Salt Inhibits Mitochondrial Complex I in Candida albicans

“…in vitro and in vivo ( 28 ). Furthermore, the inhibition effects of benzopyrylium salts on breast tumor cells and Staphylococcus aureus have already been confirmed, but their mechanism of action is still not clear ( 29 ). The antifungal effect of pyrylium salt, SM21, was first screened by Wong et al ( 16 ) Subsequent studies demonstrated that SM21 treatment results in compromised mitochondria and that SM21-resistant strains showed enhanced transcriptomic responses for peptide and protein metabolism.…”

First determination of anticancer, cytotoxic and in silico ADME evaluation of secondary metabolites of endemic Astragalus leucothrix Freyn & Bornm

“…When Kar et al, 2021 was examined, it was determined that the C2 carbon in benzopyrylium ions had a resonance between 169.20 and 179.60 ppm. Also, carbon C9 resonates between 155.90 and 167.00 ppm depending on the substituent at C6 and/or C8 [ 41 ]. However, all peaks except carbons C2 and C9 are compatible with compound 3 (3,6,8-tribromoquinoline)[ 42 – 43 ].…”

Synthesis, Characterization, In‐Vitro and In‐Vivo Anti‐Cancer Evaluation of Novel Benzopyrylium Salts on Colorectal Cancer Model of Drosophila Melanogaster

“…Considering that Carbonic Anhydrase (CA1X and XII) is predominantly present in the cancer cells, pyridinium salts have been reported to inhibit Carbonic Anhydrase isoforms II and IV, suggesting the potential development of anti‐cancer therapies [13] . The recent study on the anti‐cancer activity of Benzopyrylium salt, (E)‐3‐(2‐hydroxy‐4‐methoxybenzylidene)‐6‐methoxy‐2,3‐dihydro‐1H‐cyclopenta[b]chromen‐4‐ium chloride, [14] piqued our interest in exploring the anti‐cancer activities of this class of compounds. 3 out of 10 benzopyrylium salts discussed in this study have initially been reported solely as synthetic intermediates, with little attention given to their biological activity [15] .…”