Design, synthesis and antimalarial screening of some hybrid 4-aminoquinoline-triazine derivatives against pf-DHFR-TS

• Compound S1 showed encouraging IC50 value against 3D7 strain of Plasmodium falciparum.
• Presence of primary, secondary and tertiary amine in S1 made it most active.
• S1 showed favourable interaction with Met55, Phe58 and Leu164.

Existing antifolate antimalarial drugs have shown resistance due to the mutations at some amino acid positions of Plasmodium falciparum DHFR-TS. In the present study, to overcome this resistance, a new series of hybrid 4-aminoquinoline-triazine derivatives were designed and docked into the active site of Pf-DHFR-TS (PDB i.d. 1J3K) using validated CDOCKER protocol. Binding energy was calculated by applying CHARMm forcefield. Binding energy and the pattern of interaction of the docked compounds were analysed. Fifteen compounds were selected for synthesis based on their binding energy values and docking poses. Synthesized compounds were characterised by FTIR, 1H NMR, 13C NMR, mass spectroscopy and were screened for antimalarial activity against 3D7 strain of Plasmodium falciparum.

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