Title:Molecular Docking, Antioxidant, Anticancer and Antileishmanial Effects of Newly Synthesized Quinoline Derivatives
Volume: 20
Issue: 13
Author(s): Zoonish Malghani, Arif-Ullah Khan*, Muhammad Faheem, Muhammad Z. Danish, Humaira Nadeem, Sameen F. Ansari and Madeeha Maqbool
Affiliation:
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad,Pakistan
Keywords:
Molecular docking, anti-oxidant, anti-cancer, HepG2 cell line, HCT cell line, quinoline derivatives.
Abstract:
Background: Due to the pressing need and adverse effects associated with the available anti-cancer
agents, an attempt was made to develop the new anti-cancer agents with better activity and lesser adverse
effects.
Objective: Synthetic approaches based on chemical modification of quinoline derivatives have been undertaken
with the aim of improving anti-cancer agents’ safety profile.
Methods: In the present study, quinoline derivatives 6-hydroxy-2-(4-methoxyphenyl) quinoline-4-carboxylic
acid (M1) and 2-(4-chlorophenyl)-6-hydroxyquinoline-4-carboxylic acid (M3) were synthesized by the reaction
of aldehyde and pyruvic acid. The complete reaction was indicated by thin-layer chromatography. Newly synthesized
M1and M3were tested for in silico and in vitro studies.
Results: M1 and M3 were docked against selected targets. Both the test compounds showed good affinity against
all targets except the p300\CBP-associated factor target as there was no H-bond formed by M1. IC50 values of
M1 and M3 against 1, 1-diphenyl-picrylhydrazyl free radical scavenging activity were 562 and 136.56ng/mL,
respectively. In brine shrimp lethality assay, M1 and M3 showed IC50 value of 81.98 and 139.2ng/mL, respectively.
IC50 values recorded for M1 and M3 in tumor inhibition activity were 129 and 219μg/mL, respectively.
M1 and M3 exhibited concentration-dependent anti-cancer effects against human cell lines of hepatocellular
carcinoma (HepG2) and colon cancer (HCT-116). Against HepG2 cells, M1 and M3 exhibited IC50 of 88.6 and
43.62μg/mL, respectively. M1 and M3 utilized against HCT-116 cell lines possessed IC50 values of 62.5 and
15.3μg/mL. M1 and M3 also showed an anti-leishmanial effect with IC50 values of 336.64 and 530.142μg/mL,
respectively.
Conclusion: From the results of pharmacological studies, we conclude that the newly synthesized compound
showed enhanced anti-oxidant, anti-cancer and anti-leishmanial profile with good yield.