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Synthesis, in-vitro antiprotozoal activity and molecular docking study of isothiocyanate derivatives.
Babanezhad Harikandei, Kosar; Salehi, Peyman; Ebrahimi, Samad Nejad; Bararjanian, Morteza; Kaiser, Marcel; Al-Harrasi, Ahmed.
Afiliação
  • Babanezhad Harikandei K; Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, 1983963113 Tehran, Iran.
  • Salehi P; Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, 1983963113 Tehran, Iran. Electronic address: p-salehi@sbu.ac.ir.
  • Ebrahimi SN; Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, 1983963113 Tehran, Iran.
  • Bararjanian M; Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, 1983963113 Tehran, Iran.
  • Kaiser M; Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
  • Al-Harrasi A; National and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al-Mauz, Nizwa 611, Oman.
Bioorg Med Chem ; 28(1): 115185, 2020 01 01.
Article em En | MEDLINE | ID: mdl-31784198
ABSTRACT
Novel isothiocyanate derivatives were synthesized starting from noscapine, bile acids, amino acids, and some aromatic compounds. Antiparasitic activities of the synthesized derivatives were tested against four unicellular protozoa, i.e., Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. Interestingly, seven isothiocyanate analogues displayed promising antiparasitic activity against Leishmania donovani with IC50 values between 0.4 and 1.0 µM and selectivity index (SI) ranged from 7.8 to 18.4, comparable to the standard drug miltefosine (IC50 = 0.7 µM). Compound 7h demonstrated the best antileishmanial activity with an IC50 value of 0.4 µM. Seven products exhibited inhibition activity against T. brucei rhodesiense with IC50s below 2.0 µM and SI between 2.7 and 29.3. Four primary amine derivatives of noscapine and five isothiocyanate derivatives exhibited antiplasmodial activity with IC50s in the range of 1.1-2.7 µM and SI values between 1.1 and 14.5. The isothiocyanate derivative 7c showed against T. cruzi with an IC50 value of 1.9 µM and SI 4. Molecular docking and ADMET studies were performed to investigate the interaction between active ligands and T. brucei trypanothione reductase active site. The docking studies showed significant binding affinity of noscapine derivatives to enzyme active site and good compatibility with experimental data.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isotiocianatos / Simulação de Acoplamento Molecular / Antiprotozoários Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isotiocianatos / Simulação de Acoplamento Molecular / Antiprotozoários Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article