New Sulfanilamide Derivatives Incorporating Heterocyclic Carboxamide Moieties as Carbonic Anhydrase Inhibitors

Angeli, Andrea; Карцев, В. Г.; Petrou, Anthi; Pinteala, Mariana; Vydzhak, R. N.; Panchishin, S. Ya.; Броварец, В. С.; Luca, Viviana De; Capasso, Clemente; Geronikaki, Athina

doi:10.3390/ph14080828

Cited by 13 publications

(7 citation statements)

References 67 publications

(77 reference statements)

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“…The aim of this study is to support and extend our previous studies [51][52][53] on hCA as a target against diverse pathological conditions. Thus, herein we report the synthesis of two different groups of compounds, one of which is pyrazolo [4,3-c]pyridine sulfonamides (1a-f) and the other sulfonamide derivatives of different hetrocyclic moieties (1g-1k), and the evaluation of their inhibitory activities towards four human CAs (I, II, IX, and XII) as well as 3β and 3γ CAs from different bacterial strains.…”

Section: Introductionmentioning

confidence: 53%

Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies

Angeli

Карцев²,

Petrou

et al. 2022

Pharmaceuticals

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Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the essential reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho-/physiological conditions. A series of chromene-based sulfonamides were synthesized and tested as possible CA inhibitors. On the other hand, in microorganisms, the β- and γ- classes are expressed in addition to the α- class, showing substantial structural differences to the human isoforms. In this scenario, not only human but also bacterial CAs are of particular interest as new antibacterial agents with an alternative mechanism of action for fighting the emerging problem of extensive drug resistance afflicting most countries worldwide. Pyrazolo[4,3-c]pyridine sulfonamides were synthesized using methods of organic chemistry. Their inhibitory activity, assessed against the cytosolic human isoforms hCA I and hCA II, the transmembrane hCA IX and XII, and β- and γ-CAs from three different bacterial strains, was evaluated by a stopped-flow CO2 hydrase assay. Several of the investigated derivatives showed interesting inhibition activity towards the cytosolic associate isoforms hCA I and hCA II, as well as the 3β- and 3γ-CAs. Furthermore, computational procedures were used to investigate the binding mode of this class of compounds within the active site of hCA IX. Four compounds (1f, 1g, 1h and 1k) were more potent than AAZ against hCA I. Furthermore, compound 1f also showed better activity than AAZ against the hCA II isoform. Moreover, ten compounds out of eleven appeared to be very potent against the γ-CA from E.coli, with a Ki much lower than that of the reference drug. Most of the compounds showed better activity than AAZ against hCA I as well as the γ-CA from E.coli and the β-CA from Burkholderia pseudomallei (BpsCAβ). Compounds 1f and 1k showed a good selectivity index against hCA I and hCA XII, while 1b was selective against all 3β-CA isoforms from E.coli, BpsCA, and VhCA and all 3γ-CA isoforms from E.coli, BpsCA and PgiCA.

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Section: Introductionmentioning

confidence: 53%

Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies

Angeli

Карцев²,

Petrou

et al. 2022

Pharmaceuticals

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“…Second, compounds 103(a-o) were reacted with propargyl bromide to produce compounds N-alkyl-3-prop-2-yn-1-ylthio)-5H- [1,2,4]triazino [5,6b] indole derivatives 104(a-o) followed by the reaction with Newly synthesized compounds 105(a-o) were screened for inhibitory activity against human (h) isoforms of CA, hCA I, II, XIII (cytosolic isoforms), and hCA IX (tumor related isoform) by the stopped-flow CO 2 hydrase assay method by taking AAZ as standard drug and it was observed that 105i (X = F, R = -CH (CH 3 ) 2 ) was found to show potent activity against hCA II and hCA XIII with K i values of 7.7 and 34.9 nM, respectively, as compared to AAZ (K i = 12.1 nM) due to the presence of fluoro-group at fifth position of indole moiety and isopropyl group attached to nitrogen of indole ring [34] (Scheme 15). (110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129).…”

Section: S C H E M E Synthesis Of 94(a-s)mentioning

confidence: 99%

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

Bendi,

Taruna,

Rajni

et al. 2024

Archiv der Pharmazie

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Nowadays, the scientific community has focused on dealing with different kinds of diseases by exploring the chemistry of various heterocycles as novel drugs. In this connection, medicinal chemists identified carbonic anhydrases (CA) as one of the biologically active targets for curing various diseases. The widespread distribution of these enzymes and the high degree of homology shared by the different isoforms offer substantial challenges to discovering potential drugs. Medicinal and synthetic organic chemists have been continuously involved in developing CA inhibitors. This review explored the chemistry of different heterocycles as CA inhibitors using the last 11 years of published research work. It provides a pathway for young researchers to further explore the chemistry of a variety of synthetic as well as natural heterocycles as CA inhibitors.

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“…The m structure of these compounds is shown in Figure 4. The derivatives 1-24 and A are either simple aromatic or heterocyclic sulfonamides, and are frequently building blocks to create novel potent and selective pharmaceuticals [43,44]. T AAZ-EPA (see Table 1 for their identification) involves classical CA inhibitors (CA in clinics for managing and treating glaucoma, idiopathic intracranial hype altitude sickness, congestive heart failure, epilepsy, and other diseases [4,[36][37][38]4 Among nonantibiotic sulfonamides, primary sulfonamides (R'-SO 2 -NH 2 ) showed the most promising results due to their Zn(II) ion-binding properties; thus, they have received increased attention due to their capability to specifically inhibit CAs [42].…”

Section: Inhibition Profile Of Mpaca With Sulfonamidesmentioning

confidence: 99%

“…The molecular structure of these compounds is shown in Figure 4. The derivatives 1-24 and AAZ-EPA are either simple aromatic or heterocyclic sulfonamides, and are frequently used as building blocks to create novel potent and selective pharmaceuticals [43,44]. The series AAZ-EPA (see Table 1 for their identification) involves classical CA inhibitors (CAIs) used in clinics for managing and treating glaucoma, idiopathic intracranial hypertension, altitude sickness, congestive heart failure, epilepsy, and other diseases [4,[36][37][38]43,45].…”

Section: Inhibition Profile Of Mpaca With Sulfonamidesmentioning

confidence: 99%

Inhibitory Effects of Sulfonamide Derivatives on the β-Carbonic Anhydrase (MpaCA) from Malassezia pachydermatis, a Commensal, Pathogenic Fungus Present in Domestic Animals

Luca

Angeli

Mazzone

et al. 2021

IJMS

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Fungi are exposed to various environmental variables during their life cycle, including changes in CO2 concentration. CO2 has the potential to act as an activator of several cell signaling pathways. In fungi, the sensing of CO2 triggers cell differentiation and the biosynthesis of proteins involved in the metabolism and pathogenicity of these microorganisms. The molecular machineries involved in CO2 sensing constitute a promising target for the development of antifungals. Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial enzymes in the CO2 sensing systems of fungi, because they catalyze the reversible hydration of CO2 to proton and HCO3-. Bicarbonate in turn boots a cascade of reactions triggering fungal pathogenicity and metabolism. Accordingly, CAs affect microorganism proliferation and may represent a potential therapeutic target against fungal infection. Here, the inhibition of the unique β-CA (MpaCA) encoded in the genome of Malassezia pachydermatis, a fungus with substantial relevance in veterinary and medical sciences, was investigated using a series of conventional CA inhibitors (CAIs), namely aromatic and heterocyclic sulfonamides. This study aimed to describe novel candidates that can kill this harmful fungus by inhibiting their CA, and thus lead to effective anti-dandruff and anti-seborrheic dermatitis agents. In this context, current antifungal compounds, such as the azoles and their derivatives, have been demonstrated to induce the selection of resistant fungal strains and lose therapeutic efficacy, which might be restored by the concomitant use of alternative compounds, such as the fungal CA inhibitors.

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New Sulfanilamide Derivatives Incorporating Heterocyclic Carboxamide Moieties as Carbonic Anhydrase Inhibitors

Cited by 13 publications

References 67 publications

Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies

Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

Inhibitory Effects of Sulfonamide Derivatives on the β-Carbonic Anhydrase (MpaCA) from Malassezia pachydermatis, a Commensal, Pathogenic Fungus Present in Domestic Animals

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