Synthesis, antimalarial activity and molecular docking of hybrid 4-aminoquinoline-1,3,5-triazine derivatives

Hans Raj Bhat; Udaya Pratap Singh; Anjali Thakur; Surajit Kumar Ghosh; Kabita Gogoi; Anil Prakash; Ramendra K Singh

doi:10.1016/j.exppara.2015.06.016

Synthesis, antimalarial activity and molecular docking of hybrid 4-aminoquinoline-1,3,5-triazine derivatives

Exp Parasitol. 2015 Oct:157:59-67. doi: 10.1016/j.exppara.2015.06.016. Epub 2015 Jul 9.

Authors

Hans Raj Bhat¹, Udaya Pratap Singh², Anjali Thakur³, Surajit Kumar Ghosh⁴, Kabita Gogoi⁵, Anil Prakash⁵, Ramendra K Singh⁶

Affiliations

¹ Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Science, Deemed University, Allahabad 211007, India. Electronic address: [email protected].
² Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Science, Deemed University, Allahabad 211007, India; Nucleic Acids and Antiviral Research Laboratory, Department of Chemistry, University of Allahabad, Allahabad 211002, India.
³ Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Science, Deemed University, Allahabad 211007, India.
⁴ Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, India.
⁵ Regional Medical Research Centre, ICMR, Dibrugarh 786005, India.
⁶ Nucleic Acids and Antiviral Research Laboratory, Department of Chemistry, University of Allahabad, Allahabad 211002, India.

PMID: 26164360
DOI: 10.1016/j.exppara.2015.06.016

Abstract

A series of novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized in a five-steps reaction and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Entire synthetic derivatives showed higher antimalarial activity on the sensitive strain while two compounds, viz., 9a and 9c displayed good activity against both the strains of P. falciparum. The observed activity was further substantiated by docking study on both wild and qradruple mutant type P. falciparum dihydrofolate reductase-thymidylate synthase (pf-DHFR-TS).

Keywords: 1,3,5-triazine; 4-aminoquinoline; Antimalarial; Docking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminoquinolines / chemistry*
Aminoquinolines / pharmacology*
Animals
Antimalarials / chemical synthesis
Antimalarials / chemistry*
Antimalarials / pharmacology*
Female
Ligands
Mice
Molecular Docking Simulation
Plasmodium falciparum / drug effects*
Structure-Activity Relationship
Triazines / chemistry*

Substances

Aminoquinolines
Antimalarials
Ligands
Triazines
4-aminoquinoline