5-Arylisothiazol-3(2H)-one-1,(1)-(di)oxides: A new class of selective tumor-associated carbonic anhydrases (hCA IX and XII) inhibitors

Cornelio, Benedetta; Laronze-Cochard, Marie; Miambo, Raimundo F.; Grandis, Michela De; Riccioni, Rossana; Borisova, Boryana; Dontchev, Dimitar; Machado, Carine; Ceruso, Mariangela; Fontana, Antonella; Supuran, Claudiu T.; Sápi, János

doi:10.1016/j.ejmech.2019.04.072

Cited by 13 publications

(9 citation statements)

References 49 publications

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“…A cyclic secondary sulphonamide, 1,2benzoisothiazol-3-(2H)-one-1,1-dioxide has been described as a selective hCA IX inhibitor. Inspired by the CA inhibitory activity of N-substituted [11]. Bis(3-Thiopropionic acid) 85 is chlorinated with thionyl chloride to give carbonyl chloride analog 86 which on treatment with t-butyl amine to yield corresponding amide 87. tButylamide of thiopropionic acid 87 is cyclized mediated by thionyl chloride and afforded isothiazole derivatives wherein compounds 88 and 89 are major isothiazoles formed.…”

Section: -Arylisothiazol-3(2h)-one-1(1)-(di)oxidesmentioning

confidence: 99%

Synthesis, pharmacological evaluation and structure-activity relationship of recently discovered enzyme antagonist azoles

Dorababu¹

2020

Heliyon

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Global people are suffering from the legion of diseases. Cytotoxic property of the chemical compound would not solely influence effective drug properties and reduce unnecessary side effects. Proteins/enzymes responsible for microbe proliferation or survival are specifically targeted and inhibited successfully making the cells to undergo apoptosis. Furthermore, isoforms of essential enzymes have distinct physiological functions; thereby inhibition of essential enzyme isoforms is an apt way to the clinical approach of disease neutralization. Drugs are designed so as to play significant roles such as signaling pathways in the oncogenic process including cell proliferation, invasion, and angiogenesis. The present review comprises collective information of the recent synthesis of various organic drug compounds in brief, which could inhibit particular enzyme. The review also covers the correlation of the structure of a drug molecule designed and its inhibitory activity. Also, the most significant enzyme inhibitors are highlighted and structural moieties/core units responsible for remarkable inhibitory values are emphasized.

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Section: -Arylisothiazol-3(2h)-one-1(1)-(di)oxidesmentioning

confidence: 99%

Synthesis, pharmacological evaluation and structure-activity relationship of recently discovered enzyme antagonist azoles

Dorababu¹

2020

Heliyon

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“…A further binding mode was also observed for thioxocoumarins, these inhibitors being found in the active site in the non-hydrolyzed form, anchoring the zinc-coordinated water through the sulfur atom of the thiolactone moiety [ 34 ]. Recently, Sapi and co-workers proposed an interesting molecular simplification of saccharin [ 35 ], a well-known scaffold employed by us and other researchers to develop hCA inhibitors [ 36 , 37 , 38 , 39 ]. Particularly, the removal of the bicyclic system of the lead compound saccharin, maintaining the 5-arylisothiazol-3(2 H )-one core as mono or dioxides at the sulfur atom, led to interesting new classes of CAIs ( Figure 2 A) [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, Sapi and co-workers proposed an interesting molecular simplification of saccharin [ 35 ], a well-known scaffold employed by us and other researchers to develop hCA inhibitors [ 36 , 37 , 38 , 39 ]. Particularly, the removal of the bicyclic system of the lead compound saccharin, maintaining the 5-arylisothiazol-3(2 H )-one core as mono or dioxides at the sulfur atom, led to interesting new classes of CAIs ( Figure 2 A) [ 35 ]. The disconnected benzene ring was bound at the carbon 5 of the five-member heterocycle arylisothiazol-3(2 H )-one.…”

Section: Introductionmentioning

confidence: 99%

Novel Insights on Human Carbonic Anhydrase Inhibitors Based on Coumalic Acid: Design, Synthesis, Molecular Modeling Investigation, and Biological Studies

Pontecorvi

Mori

Picarazzi

et al. 2022

IJMS

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Human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms IX and XII are overexpressed in solid hypoxic tumors, and they are considered as prognostic tools and therapeutic targets for cancer. Based on a molecular simplification of the well-known coumarin scaffold, we developed a new series of derivatives of the pyran-2-one core. The new compounds are endowed with potent and selective inhibitory activity against the tumor-related hCA isoforms IX and XII, in the low nanomolar range, whereas they are inactive against the two cytosolic off-targets hCA I and II. The compounds exhibiting the best hCA inhibition were further investigated against the breast adenocarcinoma cell line (MCF7) in hypoxic conditions, evaluating their ability to eventually synergize with doxorubicin. The compounds’ biocompatibility on healthy cells was also tested and confirmed on Human Gingival Fibroblasts (HGFs). Furthermore, the possible binding mode of all compounds to the active site of the tumor-associated human CA IX was investigated by computational techniques which predicted the binding conformations and the persistency of binding poses within the active site of the enzyme, furnishing relevant data for the design of tight binding inhibitors.

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“…Acetazolamide is also used for the treatment and prevention of acute mountain sickness (also known as altitude sickness) and in some types of epilepsy. [19][20][21][22] In this study, a new complex of Co(II) 3,5-difluorobenzoate (DFB) with 3-pyridinol, [Co(C 7 H 3 F 2 O 2 ) 2 (C 5 H 5 NO) 2 (H 2 O) 2 ], was synthesized and its structure was characterized by elemental analysis, Fourier-transform infrared (FT-IR) spectroscopy, and single-crystal X-ray diffraction methods. In addition, the antibacterial properties of the complex were investigated by the agar-well diffusion method against Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, spectroscopic properties, crystal structures, DFT studies, and the antibacterial and enzyme inhibitory properties of a complex of Co(II) 3,5-difluorobenzoate with 3-pyridinol

Sertçelik

2020

Journal of Chemical Research

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A new complex, [Co(DFB)2(3-Pyr)2(H2O)2] (where DFB = 3,5-difluorobenzoate, 3-Pyr = 3-pyridinol), is synthesized and characterized using different techniques (elemental analysis, Fourier transform infrared spectroscopy, and single-crystal X-ray diffraction). Looking at the crystal structure of the complexes, the cobalt atom is coordinated by two nitrogen atoms from two 3-Pyr ligands, two carboxylate oxygen atoms from two DFB anions, and two oxygen atoms from two water molecules. The complex has distorted octahedral geometry around the cobalt atom center complex and crystallizes in the P21/n space group (monoclinic system). Geometry optimization, frequency analysis, and energy quantum chemical calculations on the complex are performed by Density Functional Theory [B3LYP/6-31G (d,p) basis set] to predict the molecular properties. The novel complex is tested against the metabolic isoenzymes human carbonic anhydrases I and II. The novel complex shows Ki values of 317.26 ± 23.25 µM against hCA I and 255.41 ± 48.05 µM against hCA II; the IC50 values for these isoenzymes are 274.37 and 204.33 µM.

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5-Arylisothiazol-3(2H)-one-1,(1)-(di)oxides: A new class of selective tumor-associated carbonic anhydrases (hCA IX and XII) inhibitors

Cited by 13 publications

References 49 publications

Synthesis, pharmacological evaluation and structure-activity relationship of recently discovered enzyme antagonist azoles

Synthesis, pharmacological evaluation and structure-activity relationship of recently discovered enzyme antagonist azoles

Novel Insights on Human Carbonic Anhydrase Inhibitors Based on Coumalic Acid: Design, Synthesis, Molecular Modeling Investigation, and Biological Studies

Synthesis, spectroscopic properties, crystal structures, DFT studies, and the antibacterial and enzyme inhibitory properties of a complex of Co(II) 3,5-difluorobenzoate with 3-pyridinol

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