The in Vitro Antiplasmodial and Antiproliferative Activity of New Ferrocene-Based α-Aminocresols Targeting Hemozoin Inhibition and DNA Interaction.

摘要: The conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes action. This approach holds great promise the generation potent leads in quest therapeutic chemotypes potential overcome development clinical resistance. Herein, we present in vitro antiplasmodial and antiproliferative investigation ferrocenyl α-aminocresol conjugates assembled by amalgamation ferrocene unit an scaffold possessing antimalarial activity. compounds pursued study exhibited higher toxicity towards chemosensitive (3D7) -resistant (Dd2) strains Plasmodium falciparum parasite than human HCC70 triple-negative breast cancer cell line. Indication cross-resistance was absent evaluated against multi-resistant Dd2 strain. Structure-activity analysis revealed that phenolic hydroxy group rotatable σ bond between α-carbon NH α-amino-o-cresol skeleton are crucial biological activity compounds. Spectrophotometric techniques silico docking simulations performed on selected derivatives suggest show dual mode action involving hemozoin inhibition DNA interaction via minor-groove binding. Lastly, compound 9 a, identified as possible lead, preferential binding plasmodial isolated from 3D7 P. trophozoites over mammalian calf thymus DNA, thereby substantiating enhanced presented research demonstrates incorporating into biologically active scaffolds viable avenue fashion multimodal counter