Synthesis, anticancer evaluation, and molecular modeling study of new 2-(phenylamino)pyrazolo [1,5-a]pyrimidine analogues

被引：13

作者：

Azher, Omer A. ^{[1
]}

Hossan, Aisha ^{[2
]}

Pashameah, Rami A. ^{[3
]}

Alsoliemy, Amerah ^{[3
]}

Alharbi, Arwa ^{[3
]}

Habeebullah, Turki M. ^{[4
]}

El-Metwaly, Nashwa M. ^{[3
,5
]}

机构：

[1] Al Baha Univ, Fac Appl Biomed Sci, Dept Lab Med, Al Bahah, Saudi Arabia

[2] King Khalid Univ, Fac Sci, Dept Chem, Abha, Saudi Arabia

[3] Umm Al Qura Univ, Fac Appl Sci, Dept Chem, Mecca 24230, Saudi Arabia

[4] Umm Al Qura Univ, Custodian Two Holy Mosques Inst Hajj & Umrah Res, Dept Environm & Hlth Res, Mecca, Saudi Arabia

[5] Mansoura Univ, Fac Sci, Dept Chem, El Gomhoria St, Mansoura 35516, Egypt

来源：

ARABIAN JOURNAL OF CHEMISTRY | 2023年 / 16卷 / 01期

关键词：

3-aminopyrazoles; Pyrazolopyrimidines; Molecular modelling; MCF-7; Molecular docking; BIOLOGICAL EVALUATION; ELECTRONIC-STRUCTURE; MILD-STEEL; IN-VITRO; DERIVATIVES; INHIBITOR; DFT; IDENTIFICATION; CYTOTOXICITY; MOIETY;

D O I：

10.1016/j.arabjc.2022.104437

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The reaction of 3-amino-5-phenylaminopyrazoles 2 with 3-(dimethylamino) acrylonitrile derivatives resulted in a series of substituted pyrazolopyrimidine analogues 4 and 6. The DFT stud-ies of the isolated compounds showed that the frontier molecular orbitals energy gap was close and in the 2.65-2.81 eV range where the derivative 6b has the lowest and both of 4a and 4c have the highest values. Meanwhile, the anticancer activity of the newly synthesized pyrazolopyrimidine ana-logues have been tested against several different cell lines (MCF-7, PC3, Hep-2 and WI38). The investigated pyrazolopyrimidines showed remarkable cytotoxicity activity against the MCF-7 and Hep-2 cell lines. In comparison to the effects of 5-fluorouracil, IC50 = 10.19 +/- 0.42 and 7.19 +/- 0.47, compounds 6a-c demonstrated potential anticancer activity with IC50 values for MCF-7 (10.80 +/- 0.36-19.84 +/- 0.49 lM) and Hep-2 (8.85 +/- 0.24-12.76 +/- 0.16 lM). Important details regarding the protein's binding sites were disclosed when the produced analogues docked with the crystal structure of the KDM5A protein, which was located in the protein data library.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页数：15

共 62 条

[1] Design, synthesis and anticervical cancer activity of new benzofuran-pyrazol-hydrazono- thiazolidin-4-one hybrids as potential EGFR inhibitors and apoptosis inducing agents [J].

Abbas, Hebat-Allah S. ;

Abd El Karim, Somaia S. .

BIOORGANIC CHEMISTRY, 2019, 89

[2] Synthesis of New 1,3,4-Oxadiazole-benzimidazole Derivatives as Potential Antioxidants and Breast Cancer Inhibitors with Apoptosis Inducing Activity [J].

Abd El-Meguid, E. A. ;

Awad, H. M. ;

Anwar, M. M. .

RUSSIAN JOURNAL OF GENERAL CHEMISTRY, 2019, 89 (02) :348-356

[3] 2-Amino-5-arylazothiazole-Based Derivatives: In Vitro Cytotoxicity, Antioxidant Properties, and Bleomycin-Dependent DNA Damage [J].

Al-Anazi, Khalid M. ;

Mahmoud, Ahmed H. ;

AbulFarah, Mohammad ;

Allam, Ahmed A. ;

Fouda, Moustafa M. G. ;

Gaffer, Hatem E. .

CHEMISTRYSELECT, 2019, 4 (19) :5570-5576

[4] Pyrazolo[1,5-a]pyrimidines: A Close Look into their Synthesis and Applications [J].

Al-Azmi, Amal .

CURRENT ORGANIC CHEMISTRY, 2019, 23 (06) :721-743

[5] Anticancer drug IUdR and other 5-halogen derivatives of 2′-deoxyuridine: conformers, hydrates, and structure-activity relationships [J].

Alcolea Palafox, M. .

STRUCTURAL CHEMISTRY, 2014, 25 (01) :53-69

[6] Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity [J].

Ali, Ghada M. E. ;

Ibrahim, Diaa A. ;

Elmetwali, Amira M. ;

Ismail, Nasser S. M. .

BIOORGANIC CHEMISTRY, 2019, 86 :1-14

[7] Synthesis of a new series of pyrazolo [1,5-a]pyrimidines as CDK2 inhibitors and anti-leukemia [J].

Almehmadi, Samar J. ;

Alsaedi, Amani M. R. ;

Harras, Marwa F. ;

Farghaly, Thoraya A. .

BIOORGANIC CHEMISTRY, 2021, 117

[8] Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold [J].

Arias-Gomez, Andres ;

Godoy, Andres ;

Portilla, Jaime .

MOLECULES, 2021, 26 (09)

[9] Identification, Synthesis, and Biological Evaluation of 6-[(6R)-2-(4-Fluorophenyl)-6-(hydroxymethyl)-4,5,6, 7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one (AS1940477), a Potent p38 MAP Kinase Inhibitor [J].

Asano, Toni ;

Yamazaki, Hitoshi ;

Kasahara, Chiyoshi ;

Kubota, Hirokazu ;

Kontani, Toni ;

Harayama, Yu ;

Ohno, Kazuki ;

Mizuhara, Hidekazu ;

Yokomoto, Masaharu ;

Misumi, Keiji ;

Kinoshita, Tomohiko ;

Ohta, Mitsuaki ;

Takeuchi, Makoto .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (17) :7772-7785

[10] DENSITY-FUNCTIONAL THERMOCHEMISTRY .3. THE ROLE OF EXACT EXCHANGE [J].

BECKE, AD .

JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (07) :5648-5652

← 1 2 3 4 5 6 7 →