Title:Biological Evaluation of 2-aminothiazole Hybrid as Antimalarial and Antitrypanosomal Agents: Design and Synthesis
VOLUME: 18 ISSUE: 2
Author(s):Surender S. Jadav, Vishnu N. Badavath*, Ramesh Ganesan, Narayana M. Ganta, Dominique Besson* and Venkatesan Jayaprakash*
Affiliation:Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, Department of Chemistry, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005, Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand
Keywords:2-aminothiazole hybrid, antimalarial activity, anti-trypanosomal activity, anti-leishmanial activity, cytotoxicity
studies, molecular docking simulatin.
Abstract:
Background: A series of 2-aminothiazole schiff’s bases (1-24) were synthesized and
screened against a few neglected tropical disorders (NTDs). Compounds 12 and 14 were found to
have antitrypanosidal activity, whereas compound 14 was found to be more effective than standard
benznidazole. The antiplasmodial assay provided three specific and effective compounds (9, 12 and
24) than standard chloroquine. Compound (21) inhibited Leishmania infantum, almost similar to
Miltefosine.
Methods: All the compounds were subjected to cytotoxicity assay and none of the compounds
were found to be cytotoxicity. Molecular docking simulations revealed that four compounds (1, 9,
12 and 21) were found to similarly occupy the hydrophobic active site of trans-2-enoyl acyl carrier
protein reductase of P. falciparum (PfENR) as triclosan and outcomes were closely related to their
anti-malarial potencies.
Results and Conclusion: The screening results against T. cruzi, T. brucei, L. donovani, L. infantum,
P. falciferum and cytotoxicity assays provided a few significant to most potent compounds;
two variant class of NTDs.
