SYNTHESIS, ANTIPLASMODIAL AND ADMET STUDIES OF 4-METHYLAMINO-2-PHENYLQUINOLINE ANALOGS
Keywords:Antimalarial, Chloroquine, RKL-2 strain, Pharmacokinetics, Pfitzinger reaction, Plasmodium falciparum
Objective: Synthesis, antiplasmodial and absorption, distribution, metabolism, excretion and toxicity (ADMET) studies of 4-methylamino-2-phenylquinoline analogs.
Methods: The synthesis of 4-methylamino-2-phenylquinoline analogs 7(a-j) by reacting substituted 4-(chloromethyl)-2-phenylquinoline 6(a-c) with secondary amines to explore their antimalarial property against P. falciparum RKL-2 strain and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) properties using ACD/I-Lab 2.0. The synthesized structures were confirmed by IR, NMR and Mass spectral analysis.
Results: The results revealed that at 100 Î¼g/ml, compounds 7a, 7d and 7i were found to be potent with percentage inhibition of 88.0Â±1.1, 79.1Â±1.1, 90.2Â±0.1, respectively. The compounds 7b, 7e, 7f and 7h were moderately active with 59.9Â±1.2, 48.5Â±2.0, 35.2Â±1.1 and 52.0Â±0.3 and the remaining compounds 7c, 7g and 7j exhibited mild activity 32.2Â±1.2, 36.8Â±3.0 and 28.7Â±2.0. The absorption, distribution, metabolism, excretion and toxicity (ADMET) studies of title compounds were analyzed and found to be obeying the Lipinski rule of five and are non-toxic.
Conclusion: The C4 of quinoline ring with morpholine 7a, piperidine 7d and imidazole 7i substitutions were promising enough to be taken as lead molecules in the drug discovery of new antimalarial. The in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies of the molecules were found to be obeying the Lipinski rule of five good drug likeliness.
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