Synthesis of new series of quinoline derivatives with insecticidal effects on larval vectors of malaria and dengue diseases

Abstract

Mosquito borne diseases are on the rise because of their fast spread worldwide and the lack of effective treatments. Here we are focusing on the development of a novel anti-malarial and virucidal agent with biocidal effects also on its vectors. We have synthesized a new quinoline (4,7-dichloroquinoline) derivative which showed significant larvicidal and pupicidal properties against a malarial and a dengue vector and a lethal toxicity ranging from 4.408 µM/mL (first instar larvae) to 7.958 µM/mL (pupal populations) for Anopheles stephensi and 5.016 µM/mL (larva 1) to 10.669 µM/mL (pupae) for Aedes aegypti. In-vitro antiplasmodial efficacy of 4,7-dichloroquinoline revealed a significant growth inhibition of both sensitive strains of Plasmodium falciparum with IC50 values of 6.7 nM (CQ-s) and 8.5 nM (CQ-r). Chloroquine IC50 values, as control, were 23 nM (CQ-s), and 27.5 nM (CQ-r). In vivo antiplasmodial studies with P. falciparum infected mice showed an effect of 4,7-dichloroquinoline compared to chloroquine. The quinoline compound showed significant activity against the viral pathogen serotype 2 (DENV-2). In vitro conditions and the purified quinoline exhibited insignificant toxicity on the host system up to 100 µM/mL. Overall, 4,7-dichloroquinoline could provide a good anti-vectorial and anti-malarial agent.

Synthesis of Quinoline and Quinolin-2(1H)-one Derivatives via Nickel Boride Promoted Reductive Cyclization

“…As we discussed earlier, quinoline derivatives possess wideranging therapeutic applications including their extensive usage as antimalarial drugs. [34][35][36] To estimate the binding potency of a few newly synthesized quinoline derivatives, we have docked the selected derivatives 4h, 4n, 4p, 7f and 7g to the chloroquine binding site of the plasmodium falciparum lactate dehydrogenase 37 using AutoDockVina. 38 X-ray crystal structure of the chloroquine binding plasmodium falciparum lactate dehydrogenase (PDB code: 1CET, 2.05 Å) 37 was used as a model system for docking.…”

Crystal structure and Hirshfeld surface analysis of 8-azaniumylquinolinium tetrachloridozincate(II)

“…Quinoline and its derivatives comprise an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties, such as antimalarial (Shiraki et al, 2011;Singh et al, 2011;Murugan et al, 2022), antibacterial (Upadhayaya et al, 2009;Zeleke et al, 2020), antimicrobial (Teja et al, 2016), anti-inflammatory (Guirado et al, 2012), anticancer (Abbas et al, 2015), antidiabetic (Kulkarni et al, 2012) and antihistaminic activities (Sridevi et al, 2010). The quinoline moiety is found in many drugs and is useful in the rational design of novel bioactive molecules in medicinal chemistry.…”

Quinoline‐derivatives as privileged scaffolds for medicinal and pharmaceutical chemists: A comprehensive review

“…They have observed that compound 45 exhibited greater activity with IC 50 value 0.005 μg/ml against 3D7 strain type of P. falciparum , as compared with the standard drug chloroquine tested (IC 50 = 0.020 μg/ml; Shah et al, 2012). Murugan et al synthesized a new 4,7‐dichloroquinoline derivative, compound 46 which showed significant in vitro antimalarial activity against both CQ‐resistant ( INDO ) and CQ‐sensitive ( 3D7 ) strains of P. falciparum with IC 50 values of 6.7 and 8.5 nM, respectively (Murugan et al, 2022). Roy et al developed a series of quinolone‐imidazole hybrid compounds, which were tested for blood‐stage antimalarial activity in both drug‐sensitive ( PF3D7 ) and multidrug‐resistant ( K1 ) P. falciparum strains.…”