Development of benzene and benzothiazole-sulfonamide analogues as selective inhibitors of the tumor-associated carbonic anhydrase IX

Manzoor, Shoaib; Angeli, Andrea; Zara, Susi; Carradori, Simone; Rahman, Md. Ataur; Raza, Kausar; Supuran, Claudiu T.; Hoda, Nasimul

doi:10.1016/j.ejmech.2022.114793

Cited by 11 publications

(7 citation statements)

References 54 publications

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“…However, it is important to acknowledge that this inhibitory effect also extends to normal cells, and there is no significant difference from cisplatin. Our results align with previous studies suggesting that the integration of sulfonamide-bearing heterocycles increases the ability of the compound to inhibit the carbonic anhydrase enzyme [23][24][25][26].…”

Section: Discussionsupporting

confidence: 92%

In silico study, synthesis, and antineoplastic evaluation of thiazole-based sulfonamide derivatives and their silver complexes with expected carbonic anhydrase inhibitory activity

Naji,

Naser,

Hussein

2023

JMedLife

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This study aimed to design, synthesize, and evaluate the cytotoxic activity of novel thiazole-sulfanilamide derivatives, specifically compounds M3, M4, and M5, through molecular docking and biological assays. The synthesis utilized essential chemical compounds, including sulfanilamide, chloro-acetyl chloride, thiourea, derivatives of benzaldehyde, and silver nitrate. The docking study was carried out using Molecular Operating Environment (MOE) software, and cytotoxic activity was predicted by MTT assay. The synthesized compounds demonstrated a reduction in the viability of cancer cells. Compound M5 had an IC50 of 18.53 μg/ml against MCF-7 cells, comparable to the IC50 of cisplatin. Additionally, compounds M3 and M4 had higher S scores than acetazolamide, indicating greater binding affinity to the active pocket of the receptor. Incorporating the thiazole ring in the synthesized compound augmented their flexibility and affinity for binding to the receptor. The inclusion of the metal complex additionally heightened the compounds' capacity to impede cellular growth.

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Section: Discussionsupporting

confidence: 92%

In silico study, synthesis, and antineoplastic evaluation of thiazole-based sulfonamide derivatives and their silver complexes with expected carbonic anhydrase inhibitory activity

Naji,

Naser,

Hussein

2023

JMedLife

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“…The extraction of healthy Human Gingival Fibroblasts HGFs was carried out as previously reported [40] after having received the approval of the Local Ethical Committee of the University of Chieti (Italy; approval number. 1173, on 31/03/2016).…”

Section: Methodsmentioning

confidence: 99%

Antimalarial Agents Targeting Plasmodium falciparum Carbonic Anhydrase: Towards Artesunate Hybrid Compounds with Dual Mechanism of Action

D'Agostino,

Zara,

Carradori

et al. 2023

ChemMedChem

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Malaria continues to be a major public health challenge worldwide and, as part of the global effort toward malaria eradication, plasmodium carbonic anhydrases (CAs) have recently been proposed as potential targets for malaria treatment. In this study, a series of eight hybrid compounds combining the Artesunate core with a sulfonamide moiety were synthesized and evaluated for their inhibition potency against the widely expressed human (h) CAs I, II and the isoform from P. falciparum (PfCA). All derivatives demonstrated high inhibition potency against PfCA, achieving a KI value in the sub‐nanomolar range (0.35 nM). Two Compounds showed a selectivity index of 4.1 and 3.1, respectively, against this protozoan isoform compared to hCA II. Three Derivatives showed no cytotoxic effects on human gingival fibroblasts at 50 μM with a high killing rate against both P. falciparum and P. knowlesi strains with IC50 in the sub‐nanomolar range, providing a wide therapeutic window. Our findings suggest that these compounds may serve as promising leads for developing new antimalarial drugs and warrant further investigation, including activity against antimalarial‐resistant strains, mode of action studies, and in vivo efficacy assessment in preclinical mouse models of malaria.

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“…The cancer studies of BTA analogs have reported naphthalimide derivatives with unique benzothiazole and thiazole moieties, as well as benzofuran or benzothiazole bis‐thiazole hybrid derivatives [19,20] . Furthermore, the inhibition properties of carbonic anhydrase IX by benzothiazole‐sulfonamide derivatives have been documented in a recent study [21] . In summary, many studies have been conducted in phytoremediation studies in which sulfonate derivatives have significant potential [22,23] …”

Section: Introductionmentioning

confidence: 98%

“…[19,20] Furthermore, the inhibition properties of carbonic anhydrase IX by benzothiazole-sulfonamide derivatives have been documented in a recent study. [21] In summary, many studies have been conducted in phytoremediation studies in which sulfonate derivatives have significant potential. [22,23] Enzymes catalyze various chemical reactions are vital in metabolism.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Silico Evaluation of Amylase, Tyrosinase, and Pancreatic Lipase Inhibitions of Novel Benzothiazole‐Sulfonate Derivatives

Korkmaz,

Bursal,

Kurtay

2023

ChemistrySelect

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This paper provides a comprehensive account of the synthesis and assessment of newly developed aryl sulfonate derivatives based on benzothiazole as enzyme inhibitors, specifically focusing on their ability to target tyrosinase, amylase, and pancreatic lipase. The assessments were performed utilizing experimental (in vitro) and computational (in silico) methodologies. For this aim, nine different aryl sulfonate derivatives were synthesized. The synthesized compounds were subjected to structural characterizations by utilizing Nuclear Magnetic Resonance (1H NMR, 13C NMR) and High‐Resolution Mass Spectrometry (HRMS) studies, which provided confirmation of their structural properties. The inhibitory efficiency of the compounds was determined by measuring their 50 % inhibitory concentration (IC50) values and comparing them with the standard inhibitory compounds. According to the in vitro amylase activity, benzo[d]thiazol‐2‐yl 4‐methylbenzenesulfonate showed the best inhibition with the lowest IC50 value (43.31±4.3 μM) which was calculated to be at a close level to the IC50 value of standard acarbose (38.50±3.8 μM). Also, benzo[d]thiazol‐2‐yl 4‐bromobenzenesulfonate (22.73±4.15 μM) and benzo[d]thiazol‐2‐yl 4‐chlorobenzenesulfonate (25.28±1.95 μM) were calculated to have the lowest IC50 values and the most effective inhibition capacities against pancreatic lipase. Benzo[d]thiazol‐2‐yl 4‐fluorobenzenesulfonate and benzo[d]thiazol‐2‐yl 4‐methylbenzenesulfonate significantly exhibited superior tyrosinase inhibition compared to other derivatives and conventional kojic acid. In silico molecular docking affirmed that benzo[d]thiazol‐2‐yl naphthalene‐2‐sulfonate presented the highest binding affinities to the studied enzymes, with values of −7.8 kcal/mol for tyrosinase, −10.7 kcal/mol for pancreatic lipase, and −9.4 kcal/mol for α‐amylase. The pharmacokinetic characteristics and drug‐likeness of the synthesized sulfonate derivatives were also evaluated using absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. Density Functional Theory (DFT) calculations were employed at the DFT/B3LYP/6‐311 g(d,p) level of theory to investigate the electronic characteristics of the compounds, therefore facilitating the comprehension of the reported enzyme inhibitory actions. In summary, our research highlights the potential of benzothiazole aryl sulfonate derivatives as effective enzyme inhibitors that hold promise for therapeutic applications.

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Development of benzene and benzothiazole-sulfonamide analogues as selective inhibitors of the tumor-associated carbonic anhydrase IX

Cited by 11 publications

References 54 publications

In silico study, synthesis, and antineoplastic evaluation of thiazole-based sulfonamide derivatives and their silver complexes with expected carbonic anhydrase inhibitory activity

In silico study, synthesis, and antineoplastic evaluation of thiazole-based sulfonamide derivatives and their silver complexes with expected carbonic anhydrase inhibitory activity

Antimalarial Agents Targeting Plasmodium falciparum Carbonic Anhydrase: Towards Artesunate Hybrid Compounds with Dual Mechanism of Action

In Vitro and In Silico Evaluation of Amylase, Tyrosinase, and Pancreatic Lipase Inhibitions of Novel Benzothiazole‐Sulfonate Derivatives

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