Synthesis, molecular modelling studies of indolyl chalcone derivatives and their antimalarial activity evaluation

Abstract

Twenty one chalcone derivatives were synthesized using Claisen-Schmidt condensation, their antimalarial activity against Plasmodium falciparum was determined and quantitative structureactivity relationship (QSAR) was developed. Condensation of substituted acetophenones with various aromatic aldehydes at room temperature gave chalcones in 75-96% yield. Chalcones are secondary metabolites of terrestrial plants, precursors for the biosynthesis of flavonoids and exhibit various biological activities. Antiplasmodial IC 50 (half-maximal inhibitory concentration) activity of a compound against malaria parasites in vitro provides a good first screen for identifying the antimalarial potential of the compound. The most active compound was Trans-3-(1H-indol-3-yl)-1-(2'-hydroxyphenyl)-2-propen-1-one (1b) with IC 50 of 2.1 µM/L. Molecular mechanism was explored through in silico docking & ADMET studies.

Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review

“…There is an urgent need for the design and development of novel and potent antimalarial drugs, particularly against the Plasmodium falciparum , which causes severe malaria. Accordingly, Jyoti and co-workers reported indolyl–chalcone derivatives . All the indolyl–chalcones were evaluated for their in vitro antimalarial activity against P. falciparum , NF54 strain.…”

An Updated Review on Recent Advancements in the Diverse Biological Applications of Medicinally Privileged Scaffold: Chalcone and its derivatives

“…Indolyl-chalcone hybrid, Trans-3-(1H-indol-3-yl)-1-(2'hydroxyphenyl)-2-propen-1-one (30) was also exhibited against P. falciparum, NF54 strain. The better activity of this compound was due to the presence of the hydroxyl substituent at the second position of the phenyl group, which exhibited better IC50 value 45 The obtained compound was tested and found to be effective against chloroquine-sensitive P. falciparum 3D7 (Pf3D7) strain and chloroquine-resistant P. falciparum K1 strain, determined by using SYBR-Green-I assay 46 . The antimalarial activity of the compound (2E)-3-(3,4dimethoxyphenyl)-1-(3,4,5-trimethoxycyclohexa-1,3-diene-1yl)prop-2-en-1-one (32) was evaluated using WHO Mark III schizont maturation inhibition assay and found to be active against chloroquine-resistant P. falciparum strain 47 .…”

Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry

“…A 4-aminoquinolinyl chalcone amide in conjunction with the furano derivative ( 88 ) was active against two strains, with IC 50 values ranging from 0.004 µM to 0.07 µM [ 135 ]. Furthermore, 89 is an indole-moiety-containing chalcone that is active against malaria, with an IC 50 value of 2.5 µM [ 136 ].…”