"Integrated Synthetic And In Silico Investigation Of Indane-1,3-Dione Derivatives As Potent Inhibitors Of Plasmodium Falciparum LDH"

Abstract

In the present study, 15- Indane 1.3 dione derivatives were designed and docking studies were performed using PyRx tool by targeting Pf-LDH(1LDG) and Aspartic protease plasmepsin II (1LEE) as antimalarials.The drug likeness and ADME analysis were performed on the developed Indane 1.3 dione derivatives. The compounds with the best ADME score were then assessed by docking them against the 1LDG and 1LEE targets. Assay were performed to validate in-vitro antimalarial medication for the Plasmodium falciparum sensitive to chloroquine (3D-7).Comparing Pf-LDH(1LDG) to 1LEE, the latter target has poorer binding interactions with the amino acids Val141,Lys129,Trp128,Asp130,Asp190,Leu324,Pro181,Tyr266,Ile322,Tyr309,Thr183 and Asn263. When it comes to Schizonts, Compounds XI, XII, and XIV have demonstrated half-maximum levels of inhibition (IC₅₀) values less than 0.5 μM (or <500 nM). Compounds I, V, VII, VIII, X, XIII, and XV displayed moderate activity according to the IC₅₀ values, while compounds II, III, IV, VI, and IX demonstrated less activity.Additionally, against a strain resistant to chloroquine, three compounds exhibited IC₅₀ values that range from 9.23 to 9.56 µg/ml. Compounds XI, XII, and XIV were discovered to be effective against the Plsmodium falciparum that is sensitive to chloroquine (3D-7).