Phytochemicals of Swertia chirayita Roxb. ex Fleming against malarial dihydroorotate dehydrogenase: an in silico study

Deleted Journal, Journal Year: 2024, Volume and Issue: 1(1)

Published: Oct. 14, 2024

The global economic burden of malaria is rising and lack effective drugs against it have imposed an insurmountable challenge in designing that both affordable resistanceless. plants with ethnobotanical values are relatively safer its use a viable option as therapeutics for various demographic locations. In this regard, the chemical components plant, Swertia chirayita Roxb. ex Fleming (traditionally used antimalarial agent) were explored by multiple computational tools dihydroorotate dehydrogenase (DHODH) protein Plasmodium falciparum (PDB ID: 6GJG), causative agent disease. docking scores calculated to be − 10.220, 10.131, 10.071, 10.024, 9.905 kcal/mol top five molecules (decussatin, swerchirin, 1-hydroxy-3,5,8-trimethoxyxanthen-9- one, swertinin, chiratol), respectively native ligand possessing higher value 9.873 kcal/mol. adducts geometrically thermodynamically stable revealed several parameters extracted from 200 ns molecular dynamics simulations (MDS) verified single run 600 ns. smooth RMSD profiles cumulative MDS 2.0 μs, pointed towards sturdy nature receptor geometry limited translational or rotational motion ligands. involvement LEU11, CYS14, LEU15, CYS23, PHE27, ILE102, ARG104, TYR337, LEU340, VAL341 amino acid residues mainly hydrophobic interactions at orthosteric site observed most adducts. binding free energy changes (up 30.18 ± 4.38 kcal/mol) hinted feasibility sustained thermodynamical spontaneity forward reaction complex formation. hit could possibly disrupt inhibit normal functioning DHODH leading likely prevention cure disease recommended experimental trials.

Language: Английский

Advancements in the Synthesis of Triazolopyrimidines

Current Organic Chemistry, Journal Year: 2024, Volume and Issue: 28(20), P. 1567 - 1578

Published: June 26, 2024

: The triazolopyrimidine scaffold indeed holds a prominent place in medicinal chemistry due to its versatile pharmacological properties. Researchers have explored the and derivatives for various therapeutic applications. unique structure of has made it valuable template designing medicinally active molecules. literature is full studies showcasing synthesis biological activities compounds containing ring, either fused or coupled with other heterocycles. aim this review provide comprehensive general summary recent advancements (Year 2021 present).

Language: Английский

A comprehensive review of synthetic strategies and SAR studies for the discovery of PfDHODH inhibitors as antimalarial agents. Part 2: Non-DSM compounds

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107754 - 107754

Published: Aug. 30, 2024

Language: Английский