Design, Synthesis, Molecular Modeling Studies and Biological Evaluation of N′-Arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide Derivatives as Novel Anti-HCV Agents

被引：8

作者：

Rabbani, Sayyed Mohammad Ismaeil Mahboubi ^{[1
]}

Vahabpour, Rouhollah ^{[2
]}

Hajimahdi, Zahra ^{[1
]}

Zarghi, Afshin ^{[1
]}

机构：

[1] Shahid Beheshti Univ Med Sci, Sch Pharm, Dept Pharmaceut Chem, Tehran, Iran

[2] Shahid Beheshti Univ Med Sci, Sch Allied Med Sci, Dept Med Lab Technol, Tehran, Iran

来源：

IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH | 2019年 / 18卷 / 04期

关键词：

Synthesis; Design; 4-Oxo-1,4-dihydroquinoline-3-carbohydrazide; HCV; NS5B polymerase; Molecular modeling studies; HEPATITIS-C VIRUS; NS5B POLYMERASE; RNA-POLYMERASE; INHIBITORS; DOCKING; OPTIMIZATION; DISCOVERY; REPLICATION; UPDATE; ACIDS;

D O I：

10.22037/ijpr.2019.112186.13586

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

HCV-induced hepatitis is one of the most debilitating diseases. The limited number of anti-HCV drugs and drug-resistance necessitate developing of new scaffolds with different mode of actions. HCV non-structural protein 5B (NS5B) is an attractive target for development of novel inhibitors of HCV replication. In this paper, new N'-arylidene-6-(benzyloxy)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives were designed based on the pharmacophores of HCV NS5B active site binding inhibitors. Designed compounds were synthesized and evaluated for their inhibitory activities in a cell-based HCV replicon system assay. Among tested compounds, compounds 18 and 20 were found to be the most active (EC50 = 35 and 70 mu M, respectively) with good selectivity index (SI > 2) in the corresponding series. Molecular modeling studies showed that the designed compounds are capable of forming key coordination with the two magnesium ions as well as interactions with other key residues at the active site of HCV NS5B.

引用

页码：1790 / 1802

页数：13

共 46 条

[11] Design, synthesis, and biological evaluation with molecular dynamics study of novel pyrazolo[3,4-d]pyrimidine derivatives as anti-cancer agents [J].

Shaban, Rania M. ;

Samir, Nermin ;

Nissan, Yassin M. ;

Abouzid, Khaled A. M. .

RSC ADVANCES, 2023, 13 (25) :17074-17096

[12] Molecular Modeling, Synthesis and Biological Evaluation of N-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents [J].

Sabbah, Dima A. ;

Hasan, Shaima E. ;

Abu Khalaf, Reema ;

Bardaweel, Sanaa K. ;

Hajjo, Rima ;

Alqaisi, Khalid M. ;

Sweidan, Kamal A. ;

Al-Zuheiri, Aya M. .

MOLECULES, 2020, 25 (22)

[13] Design, Synthesis, Biological Evaluation and Molecular Modeling Study of Novel Indolizine-1-Carbonitrile Derivatives as Potential Anti-Microbial Agents [J].

Faghih-Mirzaei, Ehsan ;

Seifi, Mohammad ;

Abaszadeh, Mehdi ;

Zomorodian, Kamiar ;

Helali, Helia .

IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH, 2018, 17 (03) :883-895

[14] Synthesis, biological evaluation and molecular docking studies of tetrahydropyrido[3, 4- d ]pyrimidine derivatives as anti-leukemic agents [J].

Parashuram, V. ;

Kumari, K. Aruna ;

Mullaguri, Sai Charitha ;

Kancha, Rama Krishna ;

Mittapelli, Vasantha .

RESULTS IN CHEMISTRY, 2024, 8

[15] The design, synthesis, in vitro biological evaluation and molecular modeling of novel benzenesulfonate derivatives bearing chalcone moieties as potent anti- microtubulin polymerization agents [J].

Shen, Yu-Ning ;

Lin, Lin ;

Qiu, Han-Yue ;

Zou, Wen-Yan ;

Qian, Yong ;

Zhu, Hai-Liang .

RSC ADVANCES, 2015, 5 (30) :23767-23777

[16] Novel 1,3,4-Oxadiazole Acetamide Derivatives as Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation, and Molecular Modelling Studies [J].

Rouzi, Khouloud ;

Houssni, Imane El ;

Gumede, Njabulo J. ;

Alsalme, Ali ;

Oulmidi, Afaf ;

Karbane, Miloud El ;

Bouatia, Mustapha ;

Karrouchi, Khalid .

CHEMISTRYSELECT, 2025, 10 (12)

[17] Design, synthesis, biological evaluation and molecular modeling of novel 1,3,4-oxadiazole derivatives based on Vanillic acid as potential immunosuppressive agents [J].

Tang, Jian-Feng ;

Lv, Xian-Hai ;

Wang, Xiao-Liang ;

Sun, Jian ;

Zhang, Yan-Bin ;

Yang, Yu-Shun ;

Gong, Hai-Bin ;

Zhu, Hai-Liang .

BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (14) :4226-4236

[18] One-Pot Synthesis of Novel Hydrazono-1,3-Thiazohdin-4-One Derivatives as Anti-HIV and Anti-Tubercular Agents: Synthesis, Biological Evaluation, Molecular Modelling and Admet Studies [J].

Pasha, Mohammad Arif ;

Mondal, Sumanta ;

Panigrahi, Naresh ;

Shetye, Gauri ;

Ma, Rui ;

Franzblau, Scott G. ;

Zheng, Yong-Tang ;

Murugesan, Sankaranarayanan .

CURRENT HIV RESEARCH, 2022, 20 (03) :255-271

[19] Design, synthesis, biological evaluation and molecular docking studies of novel 3-aryl-4-anilino-2H-chromen-2-one derivatives targeting ERα as anti-breast cancer agents [J].

Luo, Guoshun ;

Chen, Mingqi ;

Lyu, Weiting ;

Zhao, Ruheng ;

Xu, Qian ;

You, Qidong ;

Xiang, Hua .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (12) :2668-2673

[20] Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents [J].

Eissa, Ibrahim H. ;

El-Naggar, Abeer M. ;

El-Hashash, Maher A. .

BIOORGANIC CHEMISTRY, 2016, 67 :43-56

← 1 2 3 4 5 →