Development of Quinoline Linked Hybrid: Synthesis Characterization and Antiparasitic Potential

Parasitic diseases have been a significant issue to world health especially in the tropical and subtropical areas, where the existing chemotherapeutic agents have proved to have limitations such as drug resistance, drug toxicity, and poor efficacy thus rendering disease control ineffective. In this regard, quinoline-based compounds have remained of significant interest based on their established antiparasitic and long-standing clinical efficacy. The current review gives an overview of the quinoline-linked hybrid molecules as the future antiparasitic agents with a focus on their design, synthesis procedures, characterizations, and biological performance. Quinoline is a privileged scaffold that possesses desirable chemical and pharmacological properties and by hybridizing with various partner pharmacophores, is a rational approach to increase potency, expand target interactions, and decrease resistance liability. The major synthetic strategies, starting with the classical quinoline-forming reactions, all the way to the current coupling, click chemistry and green methodology are addressed in the framework of efficient hybrid construction. The review also discusses in vitro and in vivo antiparasitic evaluation plans, the use of standardized measurements of potency, the evaluation of selectivity, pharmacokinetics and safety profiling. Mechanistic data on the antiparasitic activity such as inhibition of heme detoxification, impairment of mitochondrial activity, stimulation of oxidative stress, synergetic multi-target effects by partner pharmacophores is critically examined. Lastly, the existing issues, future opportunities and translation concerns are discussed, to inform rational optimization and clinical improvement. Taken together, this review highlights the potential of quinoline-based hybrids as a flexible and potent platform towards development of next-generation antiparasitic therapeutics.