دورية أكاديمية
أعرض في EDS

Mitigating the resistance of MCF-7 cancer cells to Doxorubicin under hypoxic conditions with novel coumarin based carbonic anhydrase IX and XII inhibitors.

التفاصيل البيبلوغرافية
العنوان: Mitigating the resistance of MCF-7 cancer cells to Doxorubicin under hypoxic conditions with novel coumarin based carbonic anhydrase IX and XII inhibitors.
المؤلفون: Abdelaal HI; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt., Mohamed AR; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. Electronic address: abdallaharafa@eru.edu.eg., Abo-Ashour MF; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida, Egypt., Giovannuzzi S; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy., Fahim SH; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Electronic address: samer.mohamed@pharma.cu.edu.eg., Abdel-Aziz HA; Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pahros University in Alexandria, Canal El Mahmoudia Street, Alexandria 21648, Egypt., Supuran CT; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it., Abou-Seri SM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
المصدر: Bioorganic chemistry [Bioorg Chem] 2024 Nov; Vol. 152, pp. 107759. Date of Electronic Publication: 2024 Aug 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: New York, London, Academic Press.
مواضيع طبية MeSH: Carbonic Anhydrase Inhibitors*/pharmacology , Carbonic Anhydrase Inhibitors*/chemistry , Carbonic Anhydrase Inhibitors*/chemical synthesis , Coumarins*/pharmacology , Coumarins*/chemistry , Coumarins*/chemical synthesis , Carbonic Anhydrase IX*/antagonists & inhibitors , Carbonic Anhydrase IX*/metabolism , Doxorubicin*/pharmacology , Carbonic Anhydrases*/metabolism , Drug Screening Assays, Antitumor* , Dose-Response Relationship, Drug* , Cell Proliferation*/drug effects, Humans ; MCF-7 Cells ; Structure-Activity Relationship ; Molecular Structure ; Antigens, Neoplasm/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/chemical synthesis ; Apoptosis/drug effects ; Drug Resistance, Neoplasm/drug effects ; Cell Hypoxia/drug effects
مستخلص: In the present study, the design and synthesis of novel coumarin derivatives 8a-h, 11a-d and 16a-c as potential selective inhibitors for the tumor associated human carbonic anhydrase isoforms (hCA IX and XII) was reported. All the newly synthesized derivatives showed potent to mild activity against the targeted CA IX (K I  = 0.08-9.57 µM), with selectivity indices over CA I (SI = 2.0-21.9) and over CA II (SI = 1.1-15.7). They showed similar activities against CA XII (K I  = 0.06-9.48 µM) with selectivity indices over CA I (SI = 1.4-21.2) and CA II (SI = 0.9-15.5). Compound 16b featuring sulfonamide function possessed promising inhibitory activities against the targeted isoforms CA IX and XII with K I values of 0.08 and 0.06 µM, respectively. Interestingly, it was found that using compound 16b at a nontoxic concentration as an adjuvant with Doxorubicin against MCF-7 cells enhanced the cytotoxicity under hypoxia by almost 3.5 folds; IC 50 decreased from 25.74 to 7.43 µM. Therefore, compound 16b restored the cytotoxicity of Doxorubicin against MCF-7 cells under hypoxia, almost as normoxia. Furthermore, flow cytometry analysis of a combination treatment of compound 16b and Doxorubicin to the MCF7 cell line revealed an increase in cell cycle arrest at the G2/M phase and a more efficient apoptotic effect than Doxorubicin alone. Furthermore, compound 16b showed no cytotoxicity against normal breast MCF-10A cell line (IC 50  = 296.25 µM).
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Adjuvant; Anticancer sensitization; Carbonic anhydrase; Coumarins
المشرفين على المادة: 0 (Carbonic Anhydrase Inhibitors)
0 (Coumarins)
EC 4.2.1.1 (Carbonic Anhydrase IX)
80168379AG (Doxorubicin)
EC 4.2.1.1 (carbonic anhydrase XII)
EC 4.2.1.1 (Carbonic Anhydrases)
EC 4.2.1.1 (CA9 protein, human)
0 (Antigens, Neoplasm)
0 (Antineoplastic Agents)
A4VZ22K1WT (coumarin)
تواريخ الأحداث: Date Created: 20240830 Date Completed: 20240907 Latest Revision: 20240911
رمز التحديث: 20240912
DOI: 10.1016/j.bioorg.2024.107759
PMID: 39213797
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2120
DOI:10.1016/j.bioorg.2024.107759