دورية أكاديمية
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Synthesis and evaluation of sulfonamide derivatives of quinoxaline 1,4-dioxides as carbonic anhydrase inhibitors.

التفاصيل البيبلوغرافية
العنوان: Synthesis and evaluation of sulfonamide derivatives of quinoxaline 1,4-dioxides as carbonic anhydrase inhibitors.
المؤلفون: Buravchenko GI; Gause Institute of New Antibiotics 11 B. Pirogovskaya Street Moscow 119021 Russia buravchenkogi@gmail.com krymov.s.k@gmail.com gzatonsk@gmail.com shchekotikhin@mail.ru shchekotikhin@gause-inst.ru., Scherbakov AM; Department of Experimental Tumor Biology, Institute of Carcinogenesis, Blokhin N.N. National Medical Research Center of Oncology Kashirskoe sh. 24 115522 Moscow Russia dianasalnikova08@yandex.ru alex.scherbakov@gmail.com., Krymov SK; Gause Institute of New Antibiotics 11 B. Pirogovskaya Street Moscow 119021 Russia buravchenkogi@gmail.com krymov.s.k@gmail.com gzatonsk@gmail.com shchekotikhin@mail.ru shchekotikhin@gause-inst.ru., Salnikova DI; Department of Experimental Tumor Biology, Institute of Carcinogenesis, Blokhin N.N. National Medical Research Center of Oncology Kashirskoe sh. 24 115522 Moscow Russia dianasalnikova08@yandex.ru alex.scherbakov@gmail.com., Zatonsky GV; Gause Institute of New Antibiotics 11 B. Pirogovskaya Street Moscow 119021 Russia buravchenkogi@gmail.com krymov.s.k@gmail.com gzatonsk@gmail.com shchekotikhin@mail.ru shchekotikhin@gause-inst.ru., Schols D; Rega Institute for Medical Research, KU Leuven 3000 Leuven Belgium dominique.schols@kuleuven.be., Vullo D; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence Florence Italy daniela.vullo@unifi.it claudiu.supuran@unifi.it., Supuran CT; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence Florence Italy daniela.vullo@unifi.it claudiu.supuran@unifi.it., Shchekotikhin AE; Gause Institute of New Antibiotics 11 B. Pirogovskaya Street Moscow 119021 Russia buravchenkogi@gmail.com krymov.s.k@gmail.com gzatonsk@gmail.com shchekotikhin@mail.ru shchekotikhin@gause-inst.ru.
المصدر: RSC advances [RSC Adv] 2024 Jul 23; Vol. 14 (32), pp. 23257-23272. Date of Electronic Publication: 2024 Jul 23 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101581657 Publication Model: eCollection Cited Medium: Internet ISSN: 2046-2069 (Electronic) Linking ISSN: 20462069 NLM ISO Abbreviation: RSC Adv Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Cambridge [England] : Royal Society of Chemistry, [2011]-
مستخلص: A series of sulfonamide-derived quinoxaline 1,4-dioxides were synthesized and evaluated as inhibitors of carbonic anhydrases (CA) with antiproliferative potency. Overall, the synthesized compounds demonstrated good inhibitory activity against four CA isoforms. Compound 7g exhibited favorable potency in inhibiting a CA IX isozyme with a K i value of 42.2 nM compared to the reference AAZ ( K i = 25.7 nM). Nevertheless, most of the synthesized compounds have their highest activity against CA I and CA II isoforms over CA IX and CA XII. A molecular modeling study was used for an estimation of the binding mode of the selected ligand 7g in the active site of CA IX. The most active compounds (7b, 7f, 7h, and 18) exhibited significant antiproliferative activity against MCF-7, Capan-1, DND-41, HL60, and Z138 cell lines, with IC 50 values in low micromolar concentrations. Moreover, derivatives 7a, 7e, and 8g showed similar hypoxic cytotoxic activity and selectivity compared to tirapazamine (TPZ) against adenocarcinoma cells MCF-7. The structure-activity relationships analysis revealed that the presence of a halogen atom or a sulfonamide group as substituents in the phenyl ring of quinoxaline-2-carbonitrile 1,4-dioxides was favorable for overall cytotoxicity against most of the tested cancer cell lines. Additionally, the presence of a carbonitrile fragment in position 2 of the heterocycle also had a positive effect on the antitumor properties of such derivatives against the majority of cell lines. The most potent derivative, 3-trifluoromethylquinoxaline 1,4-dioxide 7h, demonstrated higher or close antiproliferative activity compared to the reference agents, such as doxorubicin, and etoposide, with an IC 50 range of 1.3-2.1 μM. Analysis of the obtained results revealed important patterns in the structure-activity relationship. Moreover, these findings highlight the potential of selected lead sulfonamides on the quinoxaline 1,4-dioxide scaffold for further in-depth evaluation and development of chemotherapeutic agents targeting carbonic anhydrases.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
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تواريخ الأحداث: Date Created: 20240724 Latest Revision: 20240725
رمز التحديث: 20240726
مُعرف محوري في PubMed: PMC11265520
DOI: 10.1039/d4ra04548c
PMID: 39045402
قاعدة البيانات: MEDLINE
الوصف
تدمد:2046-2069
DOI:10.1039/d4ra04548c