Synthesis and Biological Screening of Pyrano[3,2-c]quinoline Analogues as Anti-inflammatory and Anticancer Agents

Abstract

A series of pyrano[3,2-]quinoline based structural analogues was synthesized using one-pot multicomponent condensation between 2,4-dihydroxy-1-methylquinoline, malononitrile, and diverse un(substituted) aromatic aldehydes. The synthesized compounds were evaluated for their anti-inflammatory and cytotoxicity activity. Initially, all the compounds were evaluated for the percent inhibition of cytokine release, and cytotoxicity activity and 50% inhibitory concentrations (IC) were also determined. Based on the primary results, it was further studied for their ability to inhibit TNF-α production in the human peripheral blood mononuclear cells (hPBMC) assay. The screening results revealed that compound, ,, and were found most active candidates of the series against both anti-inflammatory and anticancer activity. The structure-activity relationship is discussed and suggested that 3-substitution on the aryl ring at C4 position of the pyrano[3,2-]quinolone structural motif seems to be an important position for both TNF-α and IL-6 inhibition and anticancer activity as well. However, structural diversity with electron withdrawing, electron donating, sterically hindered, and heteroaryl substitution sincerely affected both the inflammation and anticancer activities.

Evaluation and in vivo efficacy study of pyrano[3,2‐c]quinoline analogues as TNF‐α inhibitors

“…In this study, development and in vivo efficacy evaluation of newly synthesized pyrano[3,2 c]quinoline derivatives as TNF‐α inhibitors are described. Based on the primary screening results (Upadhyay et al., ), the promising compounds ( 4f , 4i , 4j , and 4v ) were further evaluated for their in vivo efficacy using LPS and PDE4 and CIA assays in different mice/rat models. The outcome of the study revealed that 4v was found to be most the potent candidate of the series.…”

“…Quinoline analogues exhibit diversified biological activities depending on the structure type (Kulagowski et al, 1994;Upadhyay, Dodia, Khunt, Chaniara, & Shah, 2018). As a part of number of natural products, 2,4-dihydroxyquinoline motifs are important compounds and exert a variety of interesting pharmacological properties (J, 1974).…”

Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2‑c]quinoline Analogues

“…Pyranoquinolones and fused pyrano [3,2-c]quinolone moities are widely available in bioactive natural products, synthetic products as well as pharmaceutical agents [2]. Pyrano [3,2-c]quinolones are primarily notable for their anticancer activity [3] [4], along with antimalarial [5], antibacterial [6], antiinflammatory [7], and antifungal [8] properties. Pyrano [3,2-c]quinolone is a core structural motif present in many alkaloids possessing important therapeutic activities [9].…”

Synthesis of Pyrano[3,2‐c]quinoline‐3‐carboxaldehyde and 3‐(Ethoxymethylene)‐pyrano[3,2‐c]quinolinone and Their Chemical Behavior toward Some Nitrogen and Carbon Nucleophiles

“…Pyrano[3,2‐ c ] quinolinones were found to be active against certain immuno‐reaction diseases, in particular against immediate hypersensitivity reactions (anaphylaxis) . A series of pyrano[3,2‐ c ]quinolines advertise skillful cell growth inhibition activity and are considered as potential anticancer agents . Rings annulated to the pyranoquinolinone unit showed potential medicinal properties such as antibacterial , anticoagulant , antitumor , and microtubule‐targeting agents .…”