Synthesis and evaluation of naphthyl bearing 1,2,3-triazole analogs as antiplasmodial agents, cytotoxicity and docking studies.
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.
Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India.
Saikrishna
S
Balabadra
Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India.
MeenaKumari
M
Kotni
Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, Osmania University, Hyderabad 500007, Telangana, India. Electronic address: vijjulathamanga@gmail.com.
Vijjulatha
V
Manga
Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad 500007, Telangana, India.
Aparna Devi
AD
Allanki
Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad 500007, Telangana, India.
Rajesh
R
Prasad
Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad 500007, Telangana, India.
Puran Singh
PS
Sijwali
D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018360:Crystallography, X-Ray; D057075:Enzyme Assays; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D057809:HEK293 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D009249:NADP / Q000378:metabolism; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010963:Plasmodium falciparum / Q000187:drug effects; D011739:Pyrimethamine / Q000737:chemistry; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000981:Antiprotozoal Agents; D005493:Folic Acid Antagonists; D009281:Naphthalenes; D014230:Triazoles; D009249:NADP; D011739:Pyrimethamine
Antiplasmodial activity; Click chemistry; Cytotoxicity; Induced fit docking (IFD); Naphthyl 1,2,3-triazoles