Synthesis, modeling and biological evaluation of hybrids from pyrazolo[1,5c]pyrimidine as antileishmanial agents

被引：15

作者：

Atta, Kamal Fahmy Mohamed ^{[1
]}

Ibrahim, Tamer Mohamed ^{[2
]}

Farahat, Omaima Osman Mahmoud ^{[1
]}

Al-Shargabi, Tareq Qasem ^{[1
]}

Marei, Mohamed Gaber ^{[1
]}

Bekhit, Adnan Ahmed ^{[3
]}

El Ashry, El Sayed Helmy ^{[1
]}

机构：

[1] Univ Alexandria, Dept Chem, Fac Sci, Alexandria 21321, Egypt

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

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

来源：

FUTURE MEDICINAL CHEMISTRY | 2017年 / 9卷 / 16期

关键词：

antileishmanial activity; docking on LmPTR; pyrazolo[1,5-c]pyrimidines; PROTEIN-LIGAND DOCKING; LUNG-CANCER CELLS; GENETIC ALGORITHM; ANTIMICROBIAL ACTIVITIES; HYDRAZONE DERIVATIVES; PYRAZOLE DERIVATIVES; ANTIMALARIAL AGENTS; MANNICH-BASES; DESIGN; INHIBITORS;

D O I：

10.4155/fmc-2017-0120

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aim: A new series of pyrazolo[1,5-c]pyrimidines were synthesized by different hybridization strategies. Methodology: All structures were confirmed by IR, H-1, C-13, H-1-C-13 heteronuclear multiple-quantum correlation (HMQC) spectra and microanalysis. They were evaluated for their in vitro antileishmanial activity against miltefosine and amphotericin B deoxycholate as reference drugs. Results: The most active compounds 2a and 9a demonstrated superior potencies to miltefosine by ten-and six-fold, respectively, for the promastigote form, and by 5.5-fold for the amastigote form. Their binding scenario to Leishmania major pteridine reductase was rationalized by docking experiments. In addition, all compounds were safe for the experimental animals orally up to 150 mg/kg and parenterally up to 75 mg/kg. Conclusion: This study provides novel chemotype class for antileishmanial activity. [GRAPHICS] .

引用

页码：1913 / 1929

页数：17

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