Synthesis of novel benzenesulfonamide bearing 1,2,3-triazole linked hydroxy-trifluoromethylpyrazolines and hydrazones as selective carbonic anhydrase isoforms IX and XII inhibitors

Sharma, Vikas; Kumar, Rajiv; Bua, Silvia; Supuran, Claudiu T.; Sharma, Pawan K.

doi:10.1016/j.bioorg.2019.01.002

Cited by 38 publications

(23 citation statements)

References 54 publications

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“…Recent literature studies (Kumar et al, 2018;Sharma et al, 2019) demonstrated that 1H-1,2,3-triazole ring containing heterocycles was showing superior carbonic anhydrase inhibitors (Figure 1A).…”

Section: Introductionmentioning

confidence: 94%

Synthesis of New 1H-1,2,3-Triazole Analogs in Aqueous Medium via “Click” Chemistry: A Novel Class of Potential Carbonic Anhydrase-II Inhibitors

et al. 2021

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A series of novel 1H-1,2,3-triazole analogs (9a–j) were synthesized via “Click” chemistry and Suzuki–Miyaura cross-coupling reaction in aqueous medium. The compounds were evaluated for their carbonic anhydrase-II enzyme inhibitory activity in vitro. The synthesis of triazole 7a was accomplished using (S)-(-) ethyl lactate as a starting material. This compound (7a) underwent Suzuki–Miyaura cross-coupling reaction with different arylboronic acids in aqueous medium to afford the target molecules, 9a–j in good yields. All newly synthesized compounds were characterized by 1H NMR, 13C NMR, FT-IR, HRMS, and where applicable 19F NMR spectroscopy (9b, 9e, 9h, and 9j). The new compounds have shown moderate inhibition potential against carbonic anhydrase-II enzyme. A preliminary structure-activity relationship suggested that the presence of polar group at the 1H-1,2,3-triazole substituted phenyl ring in these derivatives (9a–j) has contributed to the overall activity of these compounds. Furthermore, via molecular docking, it was deduced that the compounds exhibit inhibitory potential through direct binding with the active site residues of carbonic anhydrase-II enzyme. This study has unraveled a new series of triazole derivatives as good inhibitors against carbonic anhydrase-II.

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Section: Introductionmentioning

confidence: 94%

Synthesis of New 1H-1,2,3-Triazole Analogs in Aqueous Medium via “Click” Chemistry: A Novel Class of Potential Carbonic Anhydrase-II Inhibitors

et al. 2021

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“…It makes diverse noncovalent interactions with active sites of enzymes and receptors in biological systems and, thus display v pharmacological activities like anti-inflammatory [33], antidepressant [34], anti-p tive [35], analgesic [36] and antiviral effect [32,37,38]. Previously, Vats et al have synthesized novel 4-functionalized 1,5-diaryl-1, zoles containing benzenesulfonamide moiety as carbonic anhydrase I, II, IV and I itors [39], while novel benzenesulfonamides bearing 1,2,3-triazole linked hydroxy romethylpyrazolines and hydrazones as selective carbonic anhydrase isoforms IX inhibitors were reported by Sharma et al [40]. Similarly, Kumar et al described synthesis of novel benzenesulfonamide containing 1,2,3-triazoles [41] and benz phonamide-bearing 1,4,5-trisubstituted-1,2,3-triazoles [42] showed potent in against human carbonic anhydrase isoforms I, II, IV and IX inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors

et al. 2022

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Carbonic anhydrase-II (CA-II) is strongly related with gastric, glaucoma, tumors, malignant brain, renal and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. With an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of twelve novel 3-phenyl-β-alanine 1,3,4-oxadiazole hybrids (4a–l), characterized by 1H- and 13C-NMR with the support of HRESIMS, and evaluated for their inhibitory activity against CA-II. The CA-II inhibition results clearly indicated that the 3-phenyl-β-alanine 1,3,4-oxadiazole derivatives 4a–l exhibited selective inhibition against CA-II. All the compounds (except 4d) exhibited good to moderate CA-II inhibitory activities with IC50 value in range of 12.1 to 53.6 µM. Among all the compounds, 4a (12.1 ± 0.86 µM), 4c (13.8 ± 0.64 µM), 4b (19.1 ± 0.88 µM) and 4h (20.7 ± 1.13 µM) are the most active hybrids against carbonic CA-II. Moreover, molecular docking was performed to understand the putative binding mode of the active compounds. The docking results indicates that these compounds block the biological activity of CA-II by nicely fitting at the entrance of the active site of CA-II. These compounds specifically mediating hydrogen bonding with Thr199, Thr200, Gln92 of CA-II.

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“…[ 4,32 ] In this context, sulfonamide SLC‐0111, bearing a ureido linker, is in phase II clinical trials for the treatment of metastatic hypoxic tumors. [ 33 ] In the light of these findings and continuing our previous work of designing various classes of heterocyclic compounds as potent CAIs, [ 27,28,34–41 ] we aimed to synthesize novel benzenesulfonamides bearing thioureido‐linked pyrazole 8 and isoxazole 9 to investigate their CA‐inhibitory profiles against cytosolic isoforms hCA I and hCA II as well as tumor‐associated transmembrane isoforms hCA IX and hCA XII (Figure 1). However, our efforts to synthesize thioureido‐linked isoxazoles 9 led to the formation of amino‐1,2,4‐thiadiazoles 10 as the final product in place of the anticipated isoxazoles 9 .…”

Section: Introductionmentioning

confidence: 99%

Novel benzenesulfonamide‐bearing pyrazoles and 1,2,4‐thiadiazoles as selective carbonic anhydrase inhibitors

Kumar

Ram

et al. 2021

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Two series comprising 20 novel benzenesulfonamides bearing thioureido‐linked pyrazole 8 and amino‐1,2,4‐thiadiazole 10 were synthesized and assayed as human carbonic anhydrase (hCA) inhibitors against isoforms I and II as well as the tumor‐associated isoforms IX and XII. Molecular modeling studies of some potent derivatives (8a, 8c, 10a, and 10c) were also performed against isoforms hCA I, II, and XII. Both the promising series of compounds were synthesized by using commercially available mtethyl ketones and sulfanilamide as the starting materials. Interestingly, this paper also reports a novel methodology for the synthesis of amino‐1,2,4‐thiadiazoles 10 using 3‐amino isoxazoles and 4‐isothiocyanatobenzenesulfonamide as reactants. The activity profile of all the newly synthesized compounds reveals that amino‐linked 1,2,4‐thiadiazoles 10 were better inhibitors of the cytosolic isoform, hCA I, as compared to thioureido‐linked pyrazoles 8. Further, hCA II was strongly inhibited by nearly all the newly synthesized sulfonamides, while all the compounds were less effective as hCA IX and XII inhibitors compared to the standard drug acetazolamide. However, in terms of selectivity, compound 8e was found to be the most selective inhibitor of hCA II, which is the isoform associated with glaucoma, edema, altitude sickness, and epilepsy.

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Synthesis of novel benzenesulfonamide bearing 1,2,3-triazole linked hydroxy-trifluoromethylpyrazolines and hydrazones as selective carbonic anhydrase isoforms IX and XII inhibitors

Cited by 38 publications

References 54 publications

Synthesis of New 1H-1,2,3-Triazole Analogs in Aqueous Medium via “Click” Chemistry: A Novel Class of Potential Carbonic Anhydrase-II Inhibitors

Synthesis of New 1H-1,2,3-Triazole Analogs in Aqueous Medium via “Click” Chemistry: A Novel Class of Potential Carbonic Anhydrase-II Inhibitors

Design, Synthesis and Molecular Docking Study of Novel 3-Phenyl-β-Alanine-Based Oxadiazole Analogues as Potent Carbonic Anhydrase II Inhibitors

Novel benzenesulfonamide‐bearing pyrazoles and 1,2,4‐thiadiazoles as selective carbonic anhydrase inhibitors

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