Authors: Bekhit A.A., Saudi M.N., Hassan A.M.M., Fahmy S.M., Ibrahim T.M., Ghareeb D., El-Seidy A.M., Al-Qallaf S.M., Habib H.J., Bekhit A.E.-D.A.
Author Affiliations: Bekhit, A.A., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt, Pharmacy Program, Pharmacology Stream, Allied Health Department, College of Health Sciences, University of Bahrain, P.O. Box 32038, Bahrain; Saudi, M.N., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Hassan, A.M.M., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Fahmy, S.M., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Ibrahim, T.M., Pharmaceutical Chemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, 33516, Egypt; Ghareeb, D., Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt; El-Seidy, A.M., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Al-Qallaf, S.M., Pharmacy Program, Pharmacology Stream, Allied Health Department, College of Health Sciences, University of Bahrain, P.O. Box 32038, Bahrain; Habib, H.J., Pharmacy Program, Pharmacology Stream, Allied Health Department, College of Health Sciences, University of Bahrain, P.O. Box 32038, Bahrain; Bekhit, A.E.-D.A., Department of Food Sciences, University of Otago, Dunedin, New Zealand
Publication Date: 2018
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 IC 50 values of 1.45 ± 0.08 μM and 2.30 ± 0.09 μM, 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. © 2018 Newlands Press.
Eshan2020-11-28T18:20:26+00:00
