Antibiotic resistance associated with various microorganisms such as Gram-positive, Gram-negative, fungal strains, and multidrug-resistant tuberculosis increases the risk of healthcare survival. Preliminary therapeutics becoming ineffective that might lead to noteworthy mortality presents a crucial challenge for the scientific community. Hence, there is an urgent need to develop hybrid compounds as antimicrobial agents by combining two or more bioactive heterocyclic moieties into a single molecular framework with fewer side effects and a unique mode of action. This review highlights the recent advances (2013-2023) in the pharmacology of rhodanine-linked quinoline hybrids as more effective antimicrobial agents. In the drug development process, linker hybrids acquire the top position due to their excellent π-stacking and Van der Waals interaction with the DNA active sites of pathogens. A molecular hybridization strategy has been optimized, indicating that combining these two bioactive moieties with an arylidene and an amino spacer linker increases the antimicrobial potential and reduces drug resistance. Moreover, the structure-activity relationship study is discussed to express the role of various functional groups in improving and decrementing antimicrobial activities for rational drug design. Also, a linker approach may accelerate the development of dynamic antimicrobial agents through molecular hybridization.
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