Convenient One-Pot Synthesis and Biological Evaluation of New 3,5-Dimethyl-1H-pyrazole-1-carbothiohydrazide Derivatives as Anti-Tumor Agents

被引:2
作者
Fouad, Marwa M. [1 ]
Elaasser, Mahmoud M. [2 ]
机构
[1] Modern Acad Engn & Technol, Basic Sci Dept, Cairo 11439, Egypt
[2] Al Azhar Univ, Reg Ctr Mycol & Biotechnol, Cairo, Egypt
来源
CHEMISTRYSELECT | 2024年 / 9卷 / 11期
关键词
Cisplatin; cytotoxic activities; ethyl cyanoacetate; pyrazole-1-carbothiohydrazide; 1,3,4-thiadiazine derivatives;
D O I
10.1002/slct.202400225
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Pyrazole compounds have garnered attention due to their potential biological and medicinal qualities. Therefore, the purpose of the research being described is to utilize 3,5-dimethyl-1H-pyrazole-1-carbothiohydrazide (1) as a starting material in a one-pot synthesis to create novel pyrazole derivatives with potential biological applications. When either ethanol or acetic acid was added, components 1 and 1,3-diphenylpropane-1,3-dione (2) reacted to produce derivative 3. Compound 1, when combined with ethanol, chemical 2, or acetyl acetone 5 and triethylamine, yielded chemicals 4 and 6 respectively. When ingredient 1 was mixed with ethyl cyanoacetate (7), stearic acid (10), or carboxylic acids 12 a-c, 9, 11, and 13 a-c were formed as a result. The equivalent 1,3,4-thiadiazine derivatives, 15 and 17, were produced when 1 was mixed with either 14 or 16. The developed compounds ' cytotoxic properties were evaluated against lung and liver cancer. Our research identified a number of interesting bioactive chemicals, among which chemical 17 exhibited the greatest effectiveness against lung and liver cancer as well as the highest selectivity index measurements. It indicated a strong IC50 value of 5.35 and 8.74 mu M, accordingly, when compared with 3.78 and 6.39 mu M for the reference medication cisplatin. Additionally, its safety for use has been confirmed. Using the building block 3,5-dimethyl-1H-pyrazole-1-carbothiohydrazide (1), we have successfully synthesized novel heterocyclic compounds containing a pyrazole moiety. This was achieved by reacting it with alpha-haloketones, carboxylic acids, 1,3-diketones, and ethyl cyanoacetate. The cytotoxic properties of the compounds produced were evaluated against liver and lung tumors. Our research has uncovered numerous noteworthy bioactive ingredients, with chemical 17 exhibiting the greatest effectiveness. image
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页数:6
相关论文
共 18 条
[1]   Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives [J].
Becerra, Diana ;
Abonia, Rodrigo ;
Castillo, Juan-Carlos .
MOLECULES, 2022, 27 (15)
[2]   Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches [J].
Bin Emran, Talha ;
Shahriar, Asif ;
Mahmud, Aar Rafi ;
Rahman, Tanjilur ;
Abir, Mehedy Hasan ;
Siddiquee, Mohd. Faijanur-Rob ;
Ahmed, Hossain ;
Rahman, Nova ;
Nainu, Firzan ;
Wahyudin, Elly ;
Mitra, Saikat ;
Dhama, Kuldeep ;
Habiballah, Mahmoud M. ;
Haque, Shafiul ;
Islam, Ariful ;
Hassan, Mohammad Mahmudul .
FRONTIERS IN ONCOLOGY, 2022, 12
[3]  
Chisolm D.R., 1991, US Patent, Patent No. [5,015,777, 5015777]
[4]   Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations [J].
Costa, Rafael Fernades ;
Turones, Larissa Cordova ;
Naves Cavalcante, Keilah Valeria ;
Rosa Junior, Ismael Aureliano ;
Xavier, Carlos Henrique ;
Rosseto, Lucimar Pinheiro ;
Napolitano, Hamilton Barbosa ;
da Silva Castro, Patricia Ferreira ;
Ferreira Neto, Marcos Luiz ;
Galvao, Gustavo Mota ;
Menegatti, Ricardo ;
Pedrino, Gustavo Rodrigues ;
Costa, Elson Alves ;
Rodrigues Martins, Jose Luis ;
Fajemiroye, James Oluwagbamigbe .
FRONTIERS IN PHARMACOLOGY, 2021, 12
[5]   ABC transporters affects tumor immune microenvironment to regulate cancer immunotherapy and multidrug resistance [J].
Fan, Jingyi ;
To, Kenneth Kin Wah ;
Chen, Zhe-Sheng ;
Fu, Liwu .
DRUG RESISTANCE UPDATES, 2023, 66
[6]  
Fouad M. M., 2023, ChemRxiv, DOI [10.26434/chemrxiv-2023-9b6v1, DOI 10.26434/CHEMRXIV-2023-9B6V1]
[7]  
Fouad Marwa M, 2023, Curr Org Synth, DOI 10.2174/1570179420666230608161444
[8]   Cancer Incidence and Trends [J].
Hulvat, Melissa C. .
SURGICAL CLINICS OF NORTH AMERICA, 2020, 100 (03) :469-481
[9]  
Jemal A, 2023, CA-CANCER J CLIN, V73, P17, DOI 10.3322/caac.217634
[10]   Pyrazole Scaffolds: Centrality in Anti-Inflammatory and Antiviral Drug Design [J].
Karati, Dipanjan ;
Mahadik, Kakasaheb Ramoo ;
Kumar, Dileep .
MEDICINAL CHEMISTRY, 2022, 18 (10) :1060-1072