Quinazoline sulfonamide derivatives targeting MicroRNA-34a/MDM4/p53 apoptotic axis with radiosensitizing activity

被引：4

作者：

Soliman, Aiten M. ^{[1
]}

Kodous, Ahmad S. ^{[2
]}

Al-Sherif, Diana A. ^{[3
]}

Ghorab, Mostafa M. ^{[1
]}

机构：

[1] Natl Ctr Radiat Res & Technol NCRRT, Drug Radiat Res Dept, Egyptian Atom Energy Author EAEA, Cairo 11787, Egypt

[2] Natl Ctr Radiat Res & Technol NCRRT, Radiat Biol Dept, Egyptian Atom Energy Author EAEA, Cairo 11787, Egypt

[3] 6th October Univ, Fac Appl Med Sci, Technol Radiol & Med Imaging, Giza 12585, Egypt

来源：

FUTURE MEDICINAL CHEMISTRY | 2024年 / 16卷 / 10期

关键词：

apoptosis; microRNA; p53; quinazoline; radiosensitizer; sulfonamide; BENZENESULFONAMIDE DERIVATIVES; COLORECTAL-CANCER; ANTICANCER AGENTS; INDUCE APOPTOSIS; SMALL MOLECULES; ANGIOGENESIS; P53; MODULATION; INHIBITORS; SENESCENCE;

D O I：

10.4155/fmc-2023-0342

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: New quinazoline benzenesulfonamide hybrids 4a-n were synthesized to determine their cytotoxicity and effect on the miR-34a/MDM4/p53 apoptotic pathway. Materials & methods: Cytotoxicity against hepatic, breast, lung and colon cancer cell lines was estimated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Compound 4d was the most potent against HepG2 and MCF-7 cancer cells, with potential apoptotic activity verified by a significant upregulation of miR-34a and p53 gene expressions. The apoptotic effect of 4d was further investigated and showed downregulation of miR-21, VEGF, STAT3 and MDM4 gene expression. Conclusion: The anticancer and apoptotic activities of 4d were enhanced post irradiation by a single dose of 8 Gy gamma-radiation. Docking analysis demonstrated a valuable affinity of 4d toward VEGFR2 and MDM4 active sites.

引用

页码：929 / 948

页数：20

共 88 条

[1] New quinazolinone-pyrimidine hybrids: Synthesis, anti-inflammatory, and ulcerogenicity studies [J].

Abbas, Safinaz E. ;

Awadallah, Fadi M. ;

Ibrahin, Nashwa A. ;

Said, Eman G. ;

Kamel, Gihan M. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 53 :141-149

[2] Synthesis of some new thiazolopyrane and thiazolopyranopyrimidine derivatives bearing a sulfonamide moiety for evaluation as anticancer and radiosensitizing agents [J].

Abou El Ella, Dalal A. ;

Ghorab, Mostafa M. ;

Heiba, Helmy I. ;

Soliman, Aiten M. .

MEDICINAL CHEMISTRY RESEARCH, 2012, 21 (09) :2395-2407

[3] Novel quinazoline-based sulfonamide derivative (3D) induces apoptosis in colorectal cancer by inhibiting JAK2-STAT3 pathway [J].

Al-Obeed, Omar ;

Vaali-Mohammed, Mansoor-Ali ;

Eldehna, Wagdy M. ;

Ai-Khayal, Khayal ;

Mahmood, Amer ;

Abdel-Aziz, Hatem A. ;

Zubaidi, Ahmed ;

Alafeefy, Ahmed ;

Abdulla, Maha ;

Ahmad, Rehan .

ONCOTARGETS AND THERAPY, 2018, 11 :3313-3322

[4] Tumour Necrosis Factor-Alpha (TNF-α)-Induced Metastatic Phenotype in Colorectal Cancer Epithelial Cells: Mechanistic Support for the Role of MicroRNA-21 [J].

Alotaibi, Aminah G. G. ;

Li, Jia V. V. ;

Gooderham, Nigel J. J. .

CANCERS, 2023, 15 (03)

[5] Discovery of Benzo[g]quinazolin benzenesulfonamide derivatives as dual EGFR/HER2 inhibitors [J].

Alsaid, Mansour S. ;

Al-Mishari, Abdullah A. ;

Soliman, Aiten M. ;

Ragab, Fatma A. ;

Ghorab, Mostafa M. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 141 :84-91

[6] Cancer and Radiation Therapy: Current Advances and Future Directions [J].

Baskar, Rajamanickam ;

Lee, Kuo Ann ;

Yeo, Richard ;

Yeoh, Kheng-Wei .

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2012, 9 (03) :193-199

[7] The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics [J].

Bautista-Sanchez, Diana ;

Arriaga-Canon, Cristian ;

Pedroza-Torres, Abraham ;

De La Rosa-Velazquez, Inti Alberto ;

Gonzalez-Barrios, Rodrigo ;

Contreras-Espinosa, Laura ;

Montiel-Manriquez, Rogelio ;

Castro-Hernandez, Clementina ;

Fragoso-Ontiveros, Veronica ;

Maria Alvarez-Gomez, Rosa ;

Herrera, Luis A. .

MOLECULAR THERAPY-NUCLEIC ACIDS, 2020, 20 :409-420

[8] p53-mediated activation of miRNA34 candidate tumor-suppressor genes [J].

Bommer, Guido T. ;

Gerin, Isabelle ;

Feng, Ying ;

Kaczorowski, Andrew J. ;

Kuick, Rork ;

Love, Robert E. ;

Zhai, Yali ;

Giordano, Thomas J. ;

Qin, Zhaohui S. ;

Moore, Bethany B. ;

MacDougald, Ormond A. ;

Cho, Kathleen R. ;

Fearon, Eric R. .

CURRENT BIOLOGY, 2007, 17 (15) :1298-1307

[9] Nasopharyngeal carcinoma: molecular biomarker discovery and progress [J].

Cho, William Chi-shing .

MOLECULAR CANCER, 2007, 6 (1)

[10]

Cooper G.M., 2023, The Cell: A Molecular Approach

← 1 2 3 4 5 6 7 8 9 →