Novel triazole-sulfonamide bearing pyrimidine moieties with carbonic anhydrase inhibitory action: Design, synthesis, computational and enzyme inhibition studies

Manzoor, Shoaib; Petreni, Andrea; Raza, Kausar; Supuran, Claudiu T.; Hoda, Nasimul

doi:10.1016/j.bmcl.2021.128249

Cited by 25 publications

(11 citation statements)

References 35 publications

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“…Recently, newly design 1,2,3-triazole-based anticancer agents have been reported along with their possible modes of actions against wide range types of molecular targets. Molecular docking studies suggested that the 1,2,3-triazole based compounds could occupy in the binding sites of DNA topoisomerase-II, 68 histone deacetylase 2 (HDAC2), 69 cyclooxygenase-2 (COX-2), 70 metalloproteinases (MMP-2 and MMP-9), 71 oncogenic kinase PAK1, 72 c-MET, 41 some cancer proteins, 73 carbonic anhydrase, 74 EGFR, 75 and glycogen synthase kinase-3 (GSK-3). 76 The significant roles of the triazole ring (presented in the molecule) in the formation of ligand-binding interactions of the triazole-containing compounds were noted from several studies.…”

Section: Roles Of the 123-triazole Ring In Ligand-anticancer Targets ...mentioning

confidence: 99%

“…41 Significance of the nitrogen atoms contained in the triazole ring was also noted for the binding of the triazole-sulfonamide compound with the carbonic anhydrase via the formation of hydrogen bonds with Asn62, Lys67, and Gln92 residues. 74 Moreover, a study on the binding modes of triazole-based aromatase inhibitors suggested that the triazole ring play role in the formation of π-π stacking interaction with the Phe221 residue of the enzyme. 61,62 In addition, the role of triazole ring in the stabilized ligand-target complex and strong inhibitory effect was noted for the binding of 1,4-disubstituted 1,2,3-triazoles within the binding pockets of the MMP-2 and MMP-9 71 as well as that of the 1,2,3-triazolyl ester of ketorolac against the oncogenic kinase PAK1.…”

Section: Roles Of the 123-triazole Ring In Ligand-anticancer Targets ...mentioning

confidence: 99%

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1,2,3-Triazole Scaffold in Recent Medicinal Applications: Synthesis and Anticancer Potentials

Pingaew,

Choomuenwai,

Leechaisit

et al. 2022

HETEROCYCLES

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Cancer is one of commonly concerned health problems globally and its management is challenging. Besides an availability of diverse classes of anticancer agents, the existing drugs are noted for their limitations such as considerable toxicities, low potency and responsiveness, drug resistance, and others. 1,2,3-Triazole is an attractive heterocyclic scaffold possessing considerable characteristics and is presented in many pharmacologically active molecules.Accordingly, attention has been given to this scaffold in the recent years, especially, in an area of anticancer drug development. In this review, a collection of recently reported triazole based anticancer agents are discussed along with their synthetic methods, proposed molecular targets, and mechanisms of actions. A summary of other recently reported biological activities is also provided. In overview, recent studies suggested that the 1,2,3-triazole based compounds could elicit their anticancer effects against several cancer cell lines via an inhibition of cancer cell growth, an induction of apoptosis, an inhibition of involved enzymes such as aromatase, kinases, and others. Some interesting results from computational studies also discussed relating to the predictions of possible molecular targets. In summary, it is suggested that the 1,2,3-triazole serves as a potential scaffold with noteworthy

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Section: Roles Of the 123-triazole Ring In Ligand-anticancer Targets ...mentioning

confidence: 99%

Section: Roles Of the 123-triazole Ring In Ligand-anticancer Targets ...mentioning

confidence: 99%

1,2,3-Triazole Scaffold in Recent Medicinal Applications: Synthesis and Anticancer Potentials

Pingaew,

Choomuenwai,

Leechaisit

et al. 2022

HETEROCYCLES

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“…In addition, many studies brought to the literature in recent years have emphasized the strong CA inhibitory activity of this group. [ 15–24 ]…”

Section: Introductionmentioning

confidence: 99%

“…In addition, many studies brought to the literature in recent years have emphasized the strong CA inhibitory activity of this group. [15][16][17][18][19][20][21][22][23][24] Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. [25] In the context of contemporary medicinal chemistry and drug discovery, and particularly during lead optimization, isosterism and bioisosterism have been very active areas of research as their principles are directly applicable to structure optimization efforts.…”

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confidence: 99%

Design, synthesis, and biological activity of novel dithiocarbamate‐methylsulfonyl hybrids as carbonic anhydrase inhibitors

Osmaniye

Türkeş

Demir

et al. 2022

Archiv der Pharmazie

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Carbonic anhydrase (CA) enzymes are involved in many physiological events. These enzymes, which contain Zn 2+ in their structure, can be easily inhibited by dithiocarbamate compounds. In addition, CA enzyme inhibitory activities are known in groups such as sulfonamide and methylsulfonyl. For this purpose, in this study, a series of 23 new dithiocarbamate-methylsulfonyl derivatives were synthesized and their CA enzyme inhibitory activities were investigated. The inhibition potentials of the obtained compounds against the human CA I and CA II enzymes were investigated by the in vitro enzyme isolation method. It is seen that the compounds show activity at the nanomolar level. Molecular docking studies of the compounds were carried out by in silico methods. The poses of compounds 2a, 2e, 2o, and 2t are presented.

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“…In light of this, structural hybridization of a benzenesulfonamide scaffold with the 1,2,3‐triazole moiety was reported for designing CA inhibitors (Manzoor et al, 2021; Sharma et al, 2019; Singh et al, 2020). Sharma et al (2019) described the synthesis of a new series of hCA inhibitors by linking hydroxy‐trifluoromethylpyrazolines and hydrazones to the benzenesulfonamide 1,2,3‐triazole scaffold.…”

Section: Introductionmentioning

confidence: 99%

Click chemistry‐based synthesis of new benzenesulfonamide derivatives bearing triazole ring as selective carbonic anhydrase II inhibitors

Ewies

Sabry

Bekheit

et al. 2022

Drug Development Research

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A series of 1,2,3‐triazol‐1‐ylbenzenesulfonamide derivatives was designed, synthesized and their ability to inhibit several carbonic anhydrase isoforms was evaluated. The basis of our design is to hybridize the benzenesulfonamide moiety widely used as a zinc‐binding group, a triazole ring as spacer with a tail of different substituted aryl moieties. The synthesis of these compounds was achieved using Cu(I)‐mediated click chemistry between the azide containing the benzenesulfonamide pharmacophore and various aryl acetylenes or 1,6‐heptadiyne through copper‐catalyzed [3+2] cycloaddition reaction. The ability the new derivatives to inhibit four human carbonic anhydrase isoforms hCA I, II, IX, and XII was evaluated. All the compounds exhibited good potency and high selectivity towards isoforms hCA I and II more than isoforms hCA IX and XII, especially for the derivatives 3c and 3j that displayed Ki of 2.8 and 3.8 nM against hCA II and a high hCA II selectivity ratio ranging from 77.6 to 3571.4 over other isoforms. All the compounds were docked in the active site of the downloaded hCA II active site and their binding pattern confirmed their significant activity by interacting of the sulfonamide moiety with zinc ion in the active site, in addition to its hydrogen bond interaction with Thr199 and Thr200. All the above‐mentioned findings pointed out towards the promising activity of the synthesized series that can be presented as a new scaffold to be further optimized as selective antiglaucoma drugs.

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Novel triazole-sulfonamide bearing pyrimidine moieties with carbonic anhydrase inhibitory action: Design, synthesis, computational and enzyme inhibition studies

Cited by 25 publications

References 35 publications

1,2,3-Triazole Scaffold in Recent Medicinal Applications: Synthesis and Anticancer Potentials

1,2,3-Triazole Scaffold in Recent Medicinal Applications: Synthesis and Anticancer Potentials

Design, synthesis, and biological activity of novel dithiocarbamate‐methylsulfonyl hybrids as carbonic anhydrase inhibitors

Click chemistry‐based synthesis of new benzenesulfonamide derivatives bearing triazole ring as selective carbonic anhydrase II inhibitors

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