Synthesis and evaluation of naphthyl bearing 1,2,3-triazole analogs as antiplasmodial agents, cytotoxicity and docking studies

Bioorg Med Chem. 2017 Jan 1;25(1):221-232. doi: 10.1016/j.bmc.2016.10.029.

Saikrishna Balabadra ¹, MeenaKumari Kotni ¹, Vijjulatha Manga ², Aparna Devi Allanki ³, Rajesh Prasad ³, Puran Singh Sijwali ³

Affiliations

1 Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India.
2 Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India. Electronic address: vijjulathamanga@gmail.com.
3 Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad 500007, Telangana, India.

PMID: 27816268 DOI: 10.1016/j.bmc.2016.10.029

Abstract

Novel series of naphthyl bearing 1,2,3-triazoles (4a-t) were synthesized and evaluated for their in vitro antiplasmodial activity against pyrimethamine (Pyr)-sensitive and resistant strains of Plasmodium falciparum. The synthesized compounds were assessed for their cytotoxicity employing human embryonic kidney cell line (HEK-293), and none of them was found to be toxic. Among them 4j, 4k, 4l, 4m, 4n, 4t exhibited significant antiplasmodial activity in both strains, of which compounds 4m, 4n and 4t (∼3.0-fold) displayed superior activity to Pyr against resistant strain. Pyr and selected compounds (4n, 4p and 4t) that repressed Parasite development also inhibited PfDHFR activity of the soluble Parasite extract, suggesting that Anti-parasitic activity of these compounds is a result of inhibition of the Parasite DHFR. In silico studies suggest that activity of these compounds might be enhanced due to π-π stacking.

Keywords

Antiplasmodial activity; Click chemistry; Cytotoxicity; Induced fit docking (IFD); Naphthyl 1,2,3-triazoles.

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