Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold

被引：52
|
作者：
Elzahabi, Heba S. A. [1 ]
Nossier, Eman S. [1 ]
Khalifa, Nagy M. [2 ]
Alasfoury, Rania A. [1 ]
El-Manawaty, May A. [3 ]
机构：
[1] Al Azhar Univ, Fac Pharm Girls, Dept Pharmaceut Chem, Cairo, Egypt
[2] King Saud Univ, Dept Pharmaceut Chem, Coll Pharm, DEDC, Riyadh 11451, Saudi Arabia
[3] Natl Res Ctr, Pharmaceut Sci Div, Dept Pharmacognosy, Cairo, Egypt
来源：
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2018年 / 33卷 / 01期
关键词：
Pyrido[2,3-d]pyrimidine derivatives; anticancer activity; EGFR; CDK4/cyclin D1; molecular docking; AGENTS; APOPTOSIS; ANTITUMOR; GROWTH;
D O I：
10.1080/14756366.2018.1437729
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50: 0.3, 6.6 and 7 mu M) relative to the standard doxorubicin (IC50: 0.6, 6.8 and 12.8 mu M), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR , EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 mu M in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.
引用
收藏
页码：546 / 557
页数：12
相关论文
共 50 条
  • [1] Synthesis and anticancer evaluation of diaryl pyrido[2,3-d]pyrimidine /alkyl substituted pyrido[2,3-d]pyrimidine derivatives as thymidylate synthase inhibitors
    Kumar, Adarsh
    Backer, Nabeel
    Paliwal, Harshali
    Singh, Ankit Kumar
    Debbaraman, Tanushree
    Singh, Vikramjeet
    Kumar, Pradeep
    BMC CHEMISTRY, 2024, 18 (01)
  • [2] Discovery of New Pyrrolo[2,3-d]pyrimidine Derivatives as Potential Multi-Targeted Kinase Inhibitors and Apoptosis Inducers
    Alotaibi, AbdulAziz A.
    Alanazi, Mohammed M.
    Rahman, A. F. M. Motiur
    PHARMACEUTICALS, 2023, 16 (09)
  • [3] Furo[2,3-d]pyrimidine based derivatives as kinase inhibitors and anticancer agents
    Aziz, Marwa A.
    Serya, Rabah A. T.
    Lasheen, Deena S.
    Abouzid, Khaled A. M.
    FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES, 2016, 2 (01) : 1 - 8
  • [4] Thieno[2,3-d]pyrimidine based derivatives as kinase inhibitors and anticancer agents
    Elrazaz, Eman Z.
    Serya, Rabah A. T.
    Ismail, Nasser S. M.
    Abou El Ella, Dalal A.
    Abouzid, Khaled A. M.
    FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES, 2015, 1 (02) : 33 - 41
  • [5] Design, molecular modeling and anticancer evaluation of thieno[2,3-d] pyrimidine derivatives as inhibitors of topoisomerase II
    El-Metwally, Souad A.
    Khalil, Ali K.
    El-Sayed, Wael M.
    BIOORGANIC CHEMISTRY, 2020, 94
  • [6] PYRIDO[2,3-D]PYRIMIDINE AND PYRANO[2,3-D]PYRIMIDINE
    CHUIGUK, VA
    PINCHUK, NA
    UKRAINSKII KHIMICHESKII ZHURNAL, 1982, 48 (10): : 1112 - 1113
  • [7] Synthesis and anticancer evaluation of novel pyrrole-pyrido[2,3-d] pyrimidine-based compounds as thymidylate synthase inhibitors
    Kumar, Adarsh
    Singh, Ankit Kumar
    Singh, Harshwardhan
    Debbaraman, Tanushree
    Pathak, Prateek
    Naumovich, Vladislav
    Grishina, Maria
    Kumar, Pradeep
    JOURNAL OF MOLECULAR STRUCTURE, 2025, 1336
  • [8] Multicomponent Approach for the Sustainable Syntheses of Pyrido[2,3-d]pyrimidine Scaffold
    Chaudhary, Ankita
    CURRENT ORGANIC CHEMISTRY, 2021, 25 (23) : 2856 - 2884
  • [9] Discovery of novel c-Met kinase inhibitors bearing a thieno[2,3-d]pyrimidine or furo[2,3-d]pyrimidine scaffold
    Zhao, Ailing
    Gao, Xin
    Wang, Yuanxiang
    Ai, Jing
    Wang, Ying
    Chen, Yi
    Geng, Meiyu
    Zhang, Ao
    BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (13) : 3906 - 3918
  • [10] Synthesis and anticancer activity of some pyrido[2,3-d]pyrimidine derivatives as apoptosis inducers and cyclin-dependent kinase inhibitors
    Abbas, Safinaz E-S
    George, Riham F.
    Samir, Eman M.
    Aref, Mostafa M. A.
    Abdel-Aziz, Hatem A.
    FUTURE MEDICINAL CHEMISTRY, 2019, 11 (18) : 2395 - 2414
12345