Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAFV600E inhibitors

被引：28
|
作者：
Wang, Shu-Fu [1 ]
Zhu, Yin-Ling [1 ]
Zhu, Ping-Ting [1 ]
Makawana, Jigar A. [1 ]
Zhang, Ya-Liang [1 ]
Zhao, Meng-Yue [1 ]
Lv, Peng-Cheng [1 ]
Zhu, Hai-Liang [1 ]
机构：
[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 21期
关键词：
BRAF(V600E) inhibitor; Pyrazole; Niacinamide; Molecular docking; 3D-QSAR; B-RAF; BRAF INHIBITORS; ONCOGENIC BRAF; KINASE; PATHWAY; TUMORS; IDENTIFICATION; NICOTINAMIDE; MELANOMA; CANCER;
D O I：
10.1016/j.bmc.2014.08.029
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：
A series of novel 5-phenyl-1H-pyrazole derivatives (5a-5u) containing niacinamide moiety were synthesized and evaluated for biological activity as potential BRAF(V600E) inhibitors. Among them, compound 5h exhibited the most potent inhibitory activity with an IC50 value of 0.33 mu Mfor BRAF(V600E) . Antiproliferative assay results indicated that compound 5h has better antiproliferative activity against WM266.4 and A375 in vitro with IC50 value of 2.63 and 3.16 mu M, respectively, being comparable with the positive control vemurafenib. Molecular docking of 5h into the BRAF(V600E) active site was performed to determine the probable binding mode. Furthermore, molecular docking and 3D QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives. (C) 2014 Published by Elsevier Ltd.
引用
收藏
页码：6201 / 6208
页数：8
相关论文
共 50 条
  • [1] Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAFV600E inhibitors
    Dong, Jing-Jun
    Li, Qing-Shan
    Wang, Shu-Fu
    Li, Cui-Yun
    Zhao, Xin
    Qiu, Han-Yue
    Zhao, Meng-Yue
    Zhu, Hai-Liang
    [J]. ORGANIC & BIOMOLECULAR CHEMISTRY, 2013, 11 (37) : 6328 - 6337
  • [2] Design, synthesis, and biological evaluation of pyrazole derivatives containing acetamide bond as potential BRAFV600E inhibitors
    Wang, Chen-Ru
    Wang, Ze-Feng
    Shi, Lu
    Wang, Zhong-Chang
    Zhu, Hai-Liang
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 28 (14) : 2382 - 2390
  • [3] Synthesis and biological evaluation of novel N-(5-phenyl-1H-pyrazol-3-yl)benzenesulfonamide derivatives as potential BRAFV600E inhibitors
    Gong, Zhen-Hua
    Yao, Jian
    Ji, Jian-Feng
    Yang, Jun
    Xiang, Tie
    Zhou, Chang-Kai
    [J]. MEDICINAL CHEMISTRY RESEARCH, 2017, 26 (10) : 2583 - 2591
  • [4] Synthesis and biological evaluation of novel N-(5-phenyl-1H-pyrazol-3-yl)benzenesulfonamide derivatives as potential BRAFV600E inhibitors
    Zhen-Hua Gong
    Jian Yao
    Jian-Feng Ji
    Jun Yang
    Tie Xiang
    Chang-Kai Zhou
    [J]. Medicinal Chemistry Research, 2017, 26 : 2583 - 2591
  • [5] Design, synthesis, and biological evaluation of novel imidazole derivatives possessing terminal sulphonamides as potential BRAFV600E inhibitors
    Ali, Eslam M. H.
    Abdel-Maksoud, Mohammed S.
    Ammar, Usama M.
    Mersal, Karim, I
    Yoo, Kyung Ho
    Jooryeong, Park
    Oh, Chang-Hyun
    [J]. BIOORGANIC CHEMISTRY, 2021, 106
  • [6] Design, synthesis and biological evaluation of novel benzo-α-pyrone containing piperazine derivatives as potential BRAFV600E inhibitors
    Chen, Long-Wang
    Wang, Ze-Feng
    Zhu, Bo
    Man, Ruo-Jun
    Liu, Yan-Dong
    Zhang, Yuan-Heng
    Wang, Bao-Zhong
    Wang, Zhong-Chang
    Zhu, Hai-Liang
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (20) : 4983 - 4991
  • [7] Synthesis, biological evaluation and 3D-QSAR study of novel 4,5-dihydro-1H-pyrazole thiazole derivatives as BRAFV600E inhibitors
    Zhao, Meng-Yue
    Yin, Yong
    Yu, Xiao-Wei
    Sangani, Chetan B.
    Wang, Shu-Fu
    Lu, Ai-Min
    Yang, Li-Fang
    Lv, Peng-Cheng
    Jiang, Ming-Guo
    Zhu, Hai-Liang
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (01) : 46 - 54
  • [8] Design, synthesis and biological evaluation of (1,3-diphenyl-1H-pyrazol-4-yl) methyl benzoate derivatives as potential BRAFV600E inhibitors
    Qin, Ya-Juan
    Xing, Man
    Zhang, Ya-Liang
    Makawana, Jigar A.
    Jiang, Ai-Qin
    Zhu, Hai-Liang
    [J]. RSC ADVANCES, 2014, 4 (95): : 52702 - 52711
  • [9] Design and biological evaluation of novel triaryl pyrazoline derivatives with dioxane moiety for selective BRAFV600E inhibition
    Li, Hong-Lin
    Su, Mi-Mi
    Xu, Yun-Jie
    Xu, Chen
    Yang, Yu-Shun
    Zhu, Hai-Liang
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 155 : 725 - 735
  • [10] Computer-aided design and synthesis of 3-carbonyl-5-phenyl-1H-pyrazole as highly selective and potent BRAFV600E and CRAF inhibitor
    Kim, Jinwoong
    Choi, Byeongha
    Im, Daseul
    Jung, Hoyong
    Moon, Hyungwoo
    Aman, Waqar
    Hah, Jung-Mi
    [J]. JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2019, 34 (01) : 1314 - 1320
12345