Multitarget‐directed therapeutics: (Urea/thiourea)₂ derivatives of diverse heterocyclic‐Lys conjugates

Abstract

The synthesis of a new small library of molecules containing bis‐urea/thiourea pendants in lysine conjugated to three different heterocycles is described. The heterocycles used in this study have benzisoxazole/piperazine/piperidine units. After a detailed antimicrobial, antioxidant, and anti‐inflammatory evaluation, it was found that the most active compounds are 10, 11, 14, 15, 18, 19 and 10, 11, 19 and 8, 9, 12, 13, 16, 17, respectively. Further, it was observed that the presence of all three entities, that is, urea/thiourea, the substituent (OMe/F), as well as the heterocycle, is highly essential for exerting potent activity. Among the heterocycles, the presence of isoxazole seems to be highly beneficial for exerting good potency. In continuation, docking studies have revealed extraordinary binding efficiency for some of the active compounds. Given their potent biological results and docking score, some of the title compounds could be potential drug candidates for microbial‐related diseases and provide a basis for future research into the development of molecules possessing multitask ability.

Bis-Amiridines as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: N-Functionalization Determines the Multitarget Anti-Alzheimer’s Activity Profile

“…Our results are in good agreement with data reported in the literature on the high antioxidant potential of the thiourea unit and its potential applicability in multitarget molecules by imparting antioxidant properties to them [ 95 , 96 ]. Recent studies also show that thiourea derivatives have an excellent ability to capture free radicals and act as antioxidants, as evidenced by their powerful scavenging of superoxide radical anions (O 2 •– ) and hydroxyl radicals (OH • ) [ 97 , 98 , 99 ].…”

Conjugation as a Tool in Therapeutics: Role of Amino Acids/Peptides-Bioactive (Including Heterocycles) Hybrid Molecules in Treating Infectious Diseases

“…The molecular docking studies were performed on the active site of 2VF5 protein, which revealed that certain conjugates interacted with proteins by π-π stacking and hydrogen bonding which also possessed good binding potency between enzyme and the ligand. Finally, the authors concluded that the existence of (thiourea/urea) 2 induced the enhanced activity, specifically the conjugates substituted by 4-F and 4-Ome as they offered the most potent results [ 185 ].…”