Organotellurium (IV) complexes as anti-malarial agents: synthesis, characterization and computational insights
Creators: name: Bhardwaj, Anisha
name: Dubey, Amit
name: Tufail, Aisha
name: Tufail, Nasir
name: Kumar, Manish
name: Garg, Sapana
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Pharmacology
subject: Biotechnology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified

description: <b>Aim:</b> To synthesize and evaluate the antimalarial and antioxidant activities of novel organotellurium (IV) thiophene-based complexes. <b>Materials &amp; methods:</b> Synthesized complexes were characterized using NMR, IR and mass spectrometry. Their biological activities were assessed using <i>in vitro</i> assays and molecular docking studies. <b>Results:</b> The complexes exhibited significant antimalarial activity against <i>Plasmodium falciparum</i>, with the highest activity observed for complexes 5b and 5e. ADMET properties confirmed their potential as therapeutic agents. The rise of drug-resistant malaria parasites underscores the critical necessity of discovering innovative and effective antimalarial agents. We successfully synthesized 2-thiophene carboxaldehyde-based Schiff base ligands through the condensation of 3-methyl-2-thiophene carboxaldehyde with o-nitroaniline, which were then transformed into novel organotellurium(IV) complexes via reaction with tellurium(IV) halides. These complexes were meticulously characterized using an array of advanced spectral techniques, including NMR, UV-Vis, mass spectrometry, FTIR, SEM, EDAX, molar conductance, PXRD and TGA, confirming their distinct distorted octahedral geometry and non-electrolytic behavior in DMSO. SEM and EDAX analyzes revealed unique surface morphologies and elemental compositions, further enriching our understanding of these compounds. The synthesized complexes demonstrated exceptional antimalarial and antioxidant activities, with complexes 5a and 5b exhibiting radical scavenging efficiencies comparable to ascorbic acid and complexes 5b and 5e showing remarkable potency against malarial agents, nearly matching the efficacy of the standard drug quinine. Molecular docking studies indicated that complexes 5b and 5e have strong binding affinities with PfNDH2, suggesting their potential to disrupt malaria parasite growth by targeting this crucial enzyme. DFT calculations and MESP analyzes provided valuable insights into the electronic properties and reactivity potentials of these complexes, aiding in the identification of key binding sites and interactions with PfNDH2. This modeling highlighted essential interactions for antimalarial activity, showcasing the diverse and favorable interaction profiles of the synthesized compounds. By conducting thorough ADMET analysis, we gained crucial insights into the pharmacokinetic and toxicological profiles of these complexes, which will inform their future development and optimization, reducing the risk of drug failure. The synthesized organotellurium(IV) thiophene-based complexes emerge as highly promising candidates for new antimalarial therapies, combining potent activity with favorable pharmacological profiles.