Design and synthesis of 6-arylpyridine-tethered sulfonamides as novel selective inhibitors of carbonic anhydrase IX with promising antitumor features toward the human colorectal cancer

Eldehna, Wagdy M.; Mohammed, Eslam Essam; Al-Ansary, Ghada H.; Berrino, Emanuela; Elbadawi, Mostafa M.; Ibrahim, Tamer M.; Jaballah, Maiy; Al-Rashood, Sara T.; Binjubair, Faizah A.; Çelik, Merve; Nocentini, Alessio; Elbarbry, Fawzy; Şahin, Fikrettin; Abdel‐Aziz, Hatem A.; Supuran, Claudiu T.; Farès, Mohamed

doi:10.1016/j.ejmech.2023.115538

Cited by 14 publications

(4 citation statements)

References 45 publications

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“…CA2 is a widely expressed carbonic anhydrase isoenzyme in the human body, playing crucial roles in regulating acid-base balance, transporting carbon dioxide, maintaining calcium ion homeostasis, protecting the digestive tract and facilitating nervous system function [20] . Although the molecular biological mechanism of CA2 promoting CRC progression remains unknown, several studies have con rmed that its expression can signi cantly inhibit the cancer cell growth [21] ; furthermore, its downregulation represents an early event in CRC development [22] . ZG16 is a protein secreted by the pancreas involved in various biological processes such as pancreatic and digestive regulation, immune modulation and intestinal microbial regulation [23] .…”

Section: Discussionmentioning

confidence: 99%

Accurate prediction of colorectal cancer diagnosis using machine learning based on immunohistochemistry pathological images

Ning,

Chi,

Meng

et al. 2024

Preprint

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Colorectal cancer (CRC) ranks as the third most prevalent tumor and the second leading cause of mortality. Early and accurate diagnosis holds significant importance in enhancing patient treatment and prognosis. Machine learning technology and bioinformatics have provided novel approaches for cancer diagnosis. This study aims to develop a CRC diagnostic model based on immunohistochemical staining image features using machine learning methods. Initially, CRC disease-specific genes were identified through bioinformatics analysis and Random Forest algorithm utilizing RNA-seq data from both GEO and TCGA databases. Subsequently, verification of these genes was performed using proteomics data from CPTAC and HPA database, resulting in identification of target proteins (AKR1B10, CA2, DHRS9, and ZG16) for further investigation. SVM algorithm was then employed to analyze and integrate the characteristics of immunohistochemical images to construct a reliable CRC diagnostic model. During the training and validation process of this model, cross-validation along with external validation methods were implemented to ensure accuracy and reliability. The results demonstrate that the established diagnostic model exhibits excellent performance in distinguishing between CRC and normal controls (accuracy rate: 0.999), thereby presenting potential prospects for clinical application. These findings are expected to provide innovative perspectives as well as methodologies for personalized diagnosis of CRC while offering more precise references for promising treatment.

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Section: Discussionmentioning

confidence: 99%

Accurate prediction of colorectal cancer diagnosis using machine learning based on immunohistochemistry pathological images

Ning,

Chi,

Meng

et al. 2024

Preprint

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“…The carboxylic acid 4 was further treated with an equimolar amount of appropriately substituted benzylamine/piperazine in MeCN solution in the presence of EDCI, obtaining the desired amides 5−24 in 43− 90% yields. 1 H and 13 C NMR and ESI-MS confirmed the structures of amides 5−24, while the purity grade was elucidated by elemental analysis.…”

mentioning

confidence: 93%

“…A bnormal cell growth and spreading into neighboring tissues are common features of solid tumors, but this overgrowing is typically not followed by an adequate delivery of oxygen and nourishment due to the inadequate tumor vasculature. 1 Hypoxia may activate angiogenesis, aggressiveness, and metastasis precesses, improving tumor survival and reducing anticancer drugs' efficiency. 2 This condition leads to significant changes in gene expressions, mediated by hypoxiainducible transcription factor (HIF-1α), promoting glycolysis to enhance cell survival.…”

mentioning

confidence: 99%

Discovery of a New Class of 1-(4-Sulfamoylbenzoyl)piperidine-4-carboxamides as Human Carbonic Anhydrase Inhibitors

Moi,

Vittorio,

Angeli

et al. 2024

ACS Med. Chem. Lett.

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A series of 1-(4-sulfamoylbenzoyl)piperidine-4-carboxamides deriving from substituted piperazines/benzylamines was designed, synthesized, and tested on human carbonic anhydrase (hCA). The inhibitory activity of the new sulfonamides was analyzed using acetazolamide (AAZ) as a standard inhibitor against hCA I, II, IX, and XII. Several sulfonamides showed both inhibitory activity at low nanomolar concentrations and selectivity against the cytosolic hCA II isoform, and the same trend was observed on the tumor-associated hCA IX and XII. The benzenesulfonamido carboxamides 11 and 15 were the most potent of the piperazino- and benzylamino-based series, respectively. Docking and molecular dynamics studies related the high selectivity of compound 11 toward the tumor-associated hCA isoforms to its capability to participate in favorable interactions within hCA IX and hCA XII active sites, whereas no such interactions were detected within both hCA I and hCA II isoforms.

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“…In continuation to our research, which deals with the discovery of novel potent anticancer agents [ 23 , 24 , 25 , 26 , 27 , 28 ], herein we utilized the fragment linking strategy to construct novel anti-proliferative agents for MCF-7 breast cancer therapy and evaluated their effectiveness on VEGFR enzyme inhibition.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Assessment of N′-(2-Oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazides as Potential Anti-Proliferative Agents toward MCF-7 Breast Cancer

Alshaye,

Elgohary,

Elkotamy

et al. 2024

Pharmaceuticals

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Breast cancer is a serious threat to the health and lives of women. Two novel series of N′-(2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazides and 1-(aryl)-3-(6-methylimidazo[2,1-b]thiazol-5-yl)ureas were designed, synthesized and investigated for their anticancer efficacy against the MCF-7 breast cell line. Three compounds of the first series showed potent activity toward MCF-7 with IC50 in the range 8.38–11.67 µM, respectively, as compared to Sorafenib (IC50 = 7.55 µM). N′-(1-butyl-2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazide inhibited VEGFR-2 with IC50 = 0.33 µM when compared with Sorafenib (IC50 = 0.09 µM). Furthermore, this compound was introduced to PCR assessment, where it increased Bax, caspase 8, caspase 9 and cytochrome C levels by 4.337-, 2.727-, 4.947- and 2.420-fold, respectively, while it decreased levels of Bcl-2, as the anti-apoptotic gene, by 0.359-fold when compared to the untreated control MCF-7. This compound was also arrested in the G2/M phase by 27.07%, compared with 11.31% for the control MCF-7. Furthermore, it induced early and late apoptosis in MCF-7. In addition, a molecular docking study in the VEGFR-2 active site was performed to assess the binding profile for the most active compounds. Moreover, ADME parameters of the targeted compounds were also evaluated.

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Design and synthesis of 6-arylpyridine-tethered sulfonamides as novel selective inhibitors of carbonic anhydrase IX with promising antitumor features toward the human colorectal cancer

Cited by 14 publications

References 45 publications

Accurate prediction of colorectal cancer diagnosis using machine learning based on immunohistochemistry pathological images

Accurate prediction of colorectal cancer diagnosis using machine learning based on immunohistochemistry pathological images

Discovery of a New Class of 1-(4-Sulfamoylbenzoyl)piperidine-4-carboxamides as Human Carbonic Anhydrase Inhibitors

Design, Synthesis and Biological Assessment of N′-(2-Oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazides as Potential Anti-Proliferative Agents toward MCF-7 Breast Cancer

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