Synthesis of 1,2,4-triazole and 1,3,4-oxadiazole derivatives as inhibitors for STAT3 enzymes of breast cancer

被引：2

作者：

Fawzy, Sherif M. ^{[1
]}

Loksha, Yasser M. ^{[2
,6
]}

El-Sadek, Mohamed ^{[3
]}

Ibrahim, Samy M. ^{[3
]}

Beshay, Botros Y. ^{[4
]}

Shamaa, Marium M. ^{[5
]}

Kothayer, Hend ^{[3
]}

机构：

[1] Sinai Univ, Fac Pharm, Dept Pharmaceut Analyt Chem, Kantara Branch, Al Ismailia, Egypt

[2] Sinai Univ, Fac Pharm, Dept Pharmaceut Chem, Al Arish Branch, Al Arish, N Sinai, Egypt

[3] Zagazig Univ, Fac Pharm, Dept Med Chem, Zagazig, Egypt

[4] Arab Acad Sci Technol & Maritime Transport, Coll Pharm, Dept Pharmaceut Chem, Alexandria, Egypt

[5] Arab Acad Sci Technol & Maritime Transport, Coll Pharm, Dept Biochem, Clin & Biol Sci Div, Alexandria 1029, Egypt

[6] Sinai Univ, Fac Pharm, Dept Pharmaceut Chem, Al Arish Branch, Al Arish 45518, N Sinai, Egypt

来源：

ARCHIV DER PHARMAZIE | 2023年 / 356卷 / 11期

关键词：

breast cancer; docking; oxadiazoles; STAT3; triazoles;

D O I：

10.1002/ardp.202300345

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Disubstituted five-membered heterocycles (1,2,4-triazole and 1,3,4 oxadiazole) were synthesized and investigated as inhibitors for signal transducer and activator of transcription 3 (STAT3) enzyme of breast cancer. 3-(Benzylthio)-5-(4-chlorobenzyl)-4H-1,2,4-triazol-4-amine (12d) was found to be the most active among the synthesized compounds with a half-maximal inhibitory concentration (IC50) value of 1.5 & mu;M on MCF7 cells and was found to show a great inhibitory effect on the STAT3 enzyme. Compounds 9a,b,d,e,f, 11, and 12a,b,f,e show IC50 values in the range of 3-12 & mu;M for the MCF7 cell line. Molecular modeling was used to investigate the biological results of the synthesized compounds. 1,2,4-Triazole and 1,3,4-oxadiazole derivatives were synthesized and investigated as novel inhibitors for the signal transducer and activator of transcription 3 enzyme of breast cancer. The highest activity among the synthesized compounds was observed for 3-(benzylthio)-5-(4-chlorobenzyl)-4H-1,2,4-triazol-4-amine (12d): X = Cl, A = N-NH2, and R3 = Bz.image

引用

页数：12

共 22 条

[1] Design and synthesis of 2-Substituted-4-benzyl-5-methylimidazoles as new potential Anti-breast cancer agents to inhibit oncogenic STAT3 functions [J].

Beshay, Botros Y. ;

Abdellatef, Amira A. ;

Loksha, Yasser M. ;

Fahmy, Salwa M. ;

Habib, Nargues S. ;

Bekhit, Alaa El-Din A. ;

Georghiou, Paris E. ;

Hayakawa, Yoshihiro ;

Bekhit, Adnan A. .

BIOORGANIC CHEMISTRY, 2021, 113

[2]

BIOVIA, 2019, DASS SYST MOL MOD SI

[3] STATs and gene regulation [J].

Darnell, JE .

SCIENCE, 1997, 277 (5332) :1630-1635

[4]

DESHMUKH AA, 1984, INDIAN J CHEM B, V23, P793

[5] Recent Update on Development of Small-Molecule STAT3 Inhibitors for Cancer Therapy: From Phosphorylation Inhibition to Protein Degradation [J].

Dong, Jinyun ;

Cheng, Xiang-Dong ;

Zhang, Wei-Dong ;

Qin, Jiang-Jiang .

JOURNAL OF MEDICINAL CHEMISTRY, 2021, 64 (13) :8884-8915

[6] Novel Hybrid 1,2,4-and 1,2,3-Triazoles Targeting Mycobacterium Tuberculosis Enoyl Acyl Carrier Protein Reductase (InhA): Design, Synthesis, and Molecular Docking [J].

El Sawy, Maged A. ;

Elshatanofy, Maram M. ;

El Kilany, Yeldez ;

Kandeel, Kamal ;

Elwakil, Bassma H. ;

Hagar, Mohamed ;

Aouad, Mohamed Reda ;

Albelwi, Fawzia Faleh ;

Rezki, Nadjet ;

Jaremko, Mariusz ;

El Ashry, El Sayed H. .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (09)

[7] Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B [J].

Hennighausen, Lothar ;

Robinson, Gertraud W. .

GENES & DEVELOPMENT, 2008, 22 (06) :711-721

[8] Revisiting signal transducer and activator of transcription 3 (STAT3) as an anticancer target and its inhibitor discovery: Where are we and where should we go? [J].

Huang, Qiuyao ;

Zhong, Yan ;

Dong, Hui ;

Zheng, Qiyao ;

Shi, Shuo ;

Zhu, Kai ;

Qu, Xinming ;

Hu, Wenhao ;

Zhang, Xiaolei ;

Wang, Yuanxiang .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 187

[9] Synthesis, Antimicrobial, and Antioxidant Screening of Aryl Acetic Acid Incorporated 1,2,4-Triazolo-1,3,4-Thiadiazole Derivatives [J].

Kamboj, Vipan Kumar ;

Kapoor, Archana ;

Jain, Sandeep .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 2019, 56 (04) :1376-1382

[10] Thietane ring as a novel protecting group [J].

Khaliullin, F. A. ;

Klen, E. E. .

RUSSIAN JOURNAL OF ORGANIC CHEMISTRY, 2009, 45 (01) :135-138

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