Synthesis, molecular modeling and biological screening of some pyrazole derivatives as antileishmanial agents

被引：25

作者：

Bekhit, Adnan A. ^{[1
,2
]}

Saudi, Manal N. ^{[1
]}

Hassan, Ahmed M. M. ^{[1
]}

Fahmy, Salwa M. ^{[1
]}

Ibrahim, Tamer M. ^{[3
]}

Ghareeb, Doaa ^{[4
]}

El-Seidy, Aya M. ^{[1
]}

Al-qallaf, Sayed M. ^{[2
]}

Habib, Huda J. ^{[2
]}

Bekhit, Alaa El-Din A. ^{[5
]}

机构：

[1] Alexandria Univ, Dept Pharmaceut Chem, Fac Pharm, Alexandria 21521, Egypt

[2] Univ Bahrain, Pharm Program, Pharmacol Stream, Allied Hlth Dept,Coll Hlth Sci, POB 32038, Zallaq, Bahrain

[3] Kafrelsheikh Univ, Pharmaceut Chem Dept, Fac Pharm, Kafr Al Sheikh 33516, Egypt

[4] Alexandria Univ, Dept Biochem, Fac Sci, Alexandria, Egypt

[5] Univ Otago, Dept Food Sci, Dunedin, New Zealand

来源：

FUTURE MEDICINAL CHEMISTRY | 2018年 / 10卷 / 19期

关键词：

antileishmanial; cytotoxicity; hydrazone; oxadiazole; Pyrazole; RBC hemolysis and acute toxicity; reverse docking; triazole; DUAL ACTING ANTIMALARIAL; PROTEIN-LIGAND DOCKING; GENETIC ALGORITHM; PTERIDINE REDUCTASE; IN-VITRO; DESIGN; ANTIBACTERIAL; ANTIFUNGAL; VALIDATION; PREDICTION;

D O I：

10.4155/fmc-2018-0058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: Novel open chain and cyclized derivatives containing pyrazole scaffold were designed, synthesized and evaluated as antileishmanial compounds. Methodology &results:In silico reverse docking experiment suggested Leishmania major pteridine reductase (Lm-PTR1) as a putative target for the synthesized compounds. In vitro antileishmanial screening against L. major promastigotes and amastigotes using miltefosine and amphotericin B as references showed that the majority of the compounds displayed activity higher than miltefosine. Compounds 3i and 5 showed the highest antileishmanial activity with IC50 values of 1.45 +/- 0.08M and 2.30 +/- 0.09M, respectively, for the amastigote form. In silico drug-likeness and toxicity predictions showed acceptable profiles for most of the compounds, which were validated by experimental toxicity studies. Conclusion: This study offers promising entities for antileishmanial activity.

引用

页码：2325 / 2344

页数：20

共 76 条

[21] Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives [J].

Domiati, Souraya ;

El-Mallah, Ahmed ;

Ghoneim, Asser ;

Bekhit, Adnan ;

Abd El Razik, Heba .

INFLAMMOPHARMACOLOGY, 2016, 24 (04) :163-172

[22] 3D-QSAR based pharmacophore modeling and virtual screening for identification of novel pteridine reductase inhibitors [J].

Dube, Divya ;

Periwal, Vinita ;

Kumar, Mukesh ;

Sharma, Sujata ;

Singh, Tej P. ;

Kaur, Punit .

JOURNAL OF MOLECULAR MODELING, 2012, 18 (05) :1701-1711

[23] Synthesis, molecular modeling and anti-inflammatory screening of novel fluorinated quinoline incorporated benzimidazole derivatives using the Pfitzinger reaction [J].

El-Feky, Said A. ;

Thabet, Hamdy Kh. ;

Ubeid, Mustafa T. .

JOURNAL OF FLUORINE CHEMISTRY, 2014, 161 :87-94

[24]

El-Hashash M. A., 2014, J CHEM ENG PROCESS T, V5

[25] Ex Vivo Red Blood Cell Hemolysis Assay for the Evaluation of pH-responsive Endosomolytic Agents for Cytosolic Delivery of Biomacromolecular Drugs [J].

Evans, Brian C. ;

Nelson, Christopher E. ;

Yu, Shann S. ;

Beavers, Kelsey R. ;

Kim, Arnold J. ;

Li, Hongmei ;

Nelson, Heather M. ;

Giorgio, Todd D. ;

Duvall, Craig L. .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2013, (73)

[26]

Faidallah H. M., 2016, J ENZYM INHIB MED CH, P1

[27] Synthesis of some new azoles with antiviral potential [J].

Farghaly, Abdel-Rahman ;

El-Kashef, Hussein .

ARKIVOC, 2006, :76-90

[28] Novel pyrazole derivatives with oxa/thiadiazolyl, pyrazolyl moieties and pyrazolo[4,3-d]-pyrimidine derivatives as potential antimicrobial and anticancer agents [J].

Hafez, Hend N. ;

El-Gazzar, Abdel-Rhman B. A. ;

Al-Hussain, Sami A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (10) :2428-2433

[29]

Hamak K. F., 2014, INT J CHEM TECH RES, V6, P324

[30]

Hanumanagoud H., 2013, Der Pharma Chem, V5, P87

← 1 2 3 4 5 6 7 8 →