6-Phenoxyl-4-aminoquinoline: synthesis and preliminary antitubercular-structure activity relationship analyses

• DOI: 10.1007/s00044-025-03402-8
• Publication Date: 2025-04-05T16:35:43Z
• Authors: Richard M. Beteck; Lesetja J. Legoabe; Phelelisiwe S. Dube; Audrey Jordaan; Digby F. Warner

Abstract Diphenyl ether and quinoline based compounds have been reported to show antibacterial activity. Against Mycobacterium tuberculosis, drug targets inhibited by diphenyl ether compounds are reportedly different from those perturbed by quinoline based antitubercular hits/drugs. Herein, we conceptualized and synthesized novel molecules incorporating quinoline and diphenyl ether moieties. The antitubercular property of the synthesized compounds were measured in vitro using Tween 80 and Tyloxapol supplemented growth media. Compounds in this study generally showed sub micromolar antitubercular activity in tween 80/albumin supplemented growth medium, and moderate to poor activity in tyloxapol/casitone supplemented growth medium. Compound 4e, havin a trimethylenediamine moiety and low melting point of 68 °C, emerged as the hit compound, possessing MIC90 value of 0.2 µM. 4e is non-cytotoxic when tested against normal human cell line, exhibiting CC50 value > 20 µM.