Background:
Quinoline analogues exhibited diversified biological activities depending on the structure
type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes
were reported as promising cytotoxic agents.
Objective:
The present study is aimed to evaluate a new series of pyrano[3,2-c]quinoline scaffolds derived from
the fusion of bioactive quinolone pharmacophore with structurally diverse aryl substituted chromene for its
cytotoxicity.
Methods:
A library of pyrano[3,2-c]quinoline analogues was prepared from one-pot multi component synthesis
using various aromatic aldehydes, malononitrile and 2,4-dihydroxy-1-methylquinoline. The new synthetics were
primarily screened for its cytotoxicity (IC50) against different human cancer cell lines in vitro. The promising
synthetics were further evaluated in vitro for their potency against different kinase activity. The promising compounds
were finally tested for their in vivo efficacy in SCID type mice HCT-116 tumor model.
Results:
The screening results revealed that compounds 4c, 4f, 4i and 4j showed promising activity in in vitro
study. However, compound 4c was found to be the most potent candidate with 23% tumor growth inhibition in
HCT-116 tumor mice model.
Conclusion:
The structure activity relationship suggested that 3-substitution on the aryl ring at C4 position of
the pyrano[3,2 c]quinolone moiety seems to have an important position for cytotoxicity activity. However, 3-
chloro substitution at C4 aryl ring showed a significant alteration of the bioactive conformer of the parent scaffold
and outcome with compound 4c as the most potent candidate of the series.
