New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation

Swain, Baijayantimala; Angeli, Andrea; Singh, Priti; Arifuddin, Mohammed

doi:10.1016/j.bmc.2020.115586

Cited by 16 publications

(7 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All CA isoforms were recombinant proteins obtained in-house, as reported earlier. 25 Cell Viability Assessment. The viability and proliferation of both cell types NHOst and MG-63 were assessed using the PrestoBlue viability assay (Invitrogen Life Technologies).…”

Section: ■ Conclusionmentioning

confidence: 99%

“…The synthesis of OF1105 was performed by activating the lipoic acid 1in situ with EDC and HOBt at room temperature and in dimethylformamide (DMF) as solvent, and adding to the reaction mixture the 6-amino sulfocoumarin 2. 25 The reaction was completed in 8 h and afforded after purification by column chromatography on silica gel the lipoyl amide OF1105 in good yield (78%) (Scheme 1).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Lipoyl-Based Antagonists of Transient Receptor Potential Cation A (TRPA1) Downregulate Osteosarcoma Cell Migration and Expression of Pro-Inflammatory Cytokines

Francesconi

Corzana

Kontogianni

et al. 2022

ACS Pharmacol. Transl. Sci.

Self Cite

View full text Add to dashboard Cite

Osteosarcoma is a heterogeneous tumor intimately linked to its microenvironment, which promotes its growth and spread. It is generally accompanied by cancer-induced bone pain (CIBP), whose main component is neuropathic pain. The TRPA1 ion channel plays a key role in metastasis and is increasingly expressed in bone cancer. Here, a novel TRPA1 inhibitor is described and tested together with two other known TRPA1 antagonists. The novel lipoyl derivative has been successfully assessed for its ability to reduce human osteosarcoma MG-63 cell viability, motility, and gene expression of the CIBP pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A putative three-dimensional (3D) model of the inhibitor covalently bound to TRPA1 is also proposed. The in vitro data suggest that the novel inhibitor described here may be highly interesting and stimulating for new strategies to treat osteosarcomas.

show abstract

Section: ■ Conclusionmentioning

confidence: 99%

mentioning

confidence: 99%

Lipoyl-Based Antagonists of Transient Receptor Potential Cation A (TRPA1) Downregulate Osteosarcoma Cell Migration and Expression of Pro-Inflammatory Cytokines

Francesconi

Corzana

Kontogianni

et al. 2022

ACS Pharmacol. Transl. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Closely related to these structures, works have been published on coumarin derivatives with inhibitory activity on carbonic anhydrase IX and XII . These are coumarins that incorporate arylacrylamide substituents at position 3 ( Figure 6 , general structure XXIV ) that showed inhibitory activity in the nanomolar range [ 38 ]. In other cases, anhydrase inhibitory activity was reported for hybrids connected by a methyleneoxy linker at position 7, oxadiazole heterocycles [ 39 ] that the same authors extend to the triazole ring ( Figure 6 , general structure XXV ) [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Trending Topics on Coumarin and Its Derivatives in 2020

et al. 2021

View full text Add to dashboard Cite

Coumarins are naturally occurring molecules with a versatile range of activities. Their structural and physicochemical characteristics make them a privileged scaffold in medicinal chemistry and chemical biology. Many research articles and reviews compile information on this important family of compounds. In this overview, the most recent research papers and reviews from 2020 are organized and analyzed, and a discussion on these data is included. Multiple electronic databases were scanned, including SciFinder, Mendeley, and PubMed, the latter being the main source of information. Particular attention was paid to the potential of coumarins as an important scaffold in drug design, as well as fluorescent probes for decaging of prodrugs, metal detection, and diagnostic purposes. Herein we do an analysis of the trending topics related to coumarin and its derivatives in the broad field of drug discovery.

show abstract

“…Besides sulfonamide derivatives, coumarins were recently shown to constitute a totally new class of inhibitors of the zinc metalloenzyme carbonic anhydrase. Coumarins have a high selectivity against trans-membrane tumour-associated hCA IX and hCA XII isoforms, compared to the widespread cytosolic hCA I and II isoforms [17,[25][26][27][28][29]. One explanation for this high selectivity against human isoforms IX and XII compared to I and II is that while the twelve catalytically-active human isoforms have a rather conserved active site, especially in the lower and median parts, the most variable region is at the entrance to the cavity, where many residues differ between the various isoforms.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Crystal Structure, Inhibitory Activity and Molecular Docking of Coumarins/Sulfonamides Containing Triazolyl Pyridine Moiety as Potent Selective Carbonic Anhydrase IX and XII Inhibitors

et al. 2021

Self Cite

View full text Add to dashboard Cite

In this work, two classes of Carbonic Anhydrase (CA) inhibitors, sulfonamide and coumarin derivatives linked to pyta moiety (2a-b) and their corresponding rhenium complexes (3a-b), were designed. These compounds were synthesized and fully characterized by classical analytical methods and X-ray diffraction. All the synthesized compounds were evaluated for their inhibitory activity against the hCA isoforms I, II, IX and XII. They exhibited high inhibitory activities in the range of nanomolar for both hCA IX and hCA XII isoforms. The sulfonamide compound 2a showed the strongest inhibition against the tumour-associated hCA IX isoform with a Ki of 11.7 nM. The tumour-associated isoforms hCA IX and hCA XII were selectively inhibited by all the coumarin derivatives, with inhibition constants ranging from 12.7 nM (2b) to 44.5 nM (3b), while the hCA I and II isoforms were slightly inhibited (in the micromolar range), as expected. In terms of selectivity, compared to previously published rhenium complex-based CA inhibitors, complex 3b showed one of the highest selectivities against hCA IX and hCA XII compared to the off-target isoforms hCA I and hCA II, making it a potential anti-cancer drug candidate. Molecular docking calculations were performed to investigate the inhibition profiles of the investigated compounds at the tumour-associated hCA IX active site and to rationalize our results.

show abstract

New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation

Cited by 16 publications

References 40 publications

Lipoyl-Based Antagonists of Transient Receptor Potential Cation A (TRPA1) Downregulate Osteosarcoma Cell Migration and Expression of Pro-Inflammatory Cytokines

Lipoyl-Based Antagonists of Transient Receptor Potential Cation A (TRPA1) Downregulate Osteosarcoma Cell Migration and Expression of Pro-Inflammatory Cytokines

Trending Topics on Coumarin and Its Derivatives in 2020

Synthesis, Crystal Structure, Inhibitory Activity and Molecular Docking of Coumarins/Sulfonamides Containing Triazolyl Pyridine Moiety as Potent Selective Carbonic Anhydrase IX and XII Inhibitors

Contact Info

Product

Resources

About