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

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