Neoflavonoids and tetrahydroquinolones as possible cancer chemopreventive agents.
Several lactone- and lactam-based neoflavonoids and tetrahydroquinolones were synthesized and evaluated for cancer chemopreventive studies using cell and molecular target-based in vitro bioassays, namely NFκB, aromatase, and quinone reductase 1. These analogs blocked TNF-α-induced NFκB activation in a dose-dependent manner with IC₅₀ values in the range of 0.11-3.2 μM. In addition, compound 8 inhibited aromatase activity with an IC₅₀ value of 12.12 μM, and compound 10 affected quinone reductase 1 induction (IR, 3.6; CD, 19.57 μM). Neoflavonoids 8 and 10 exhibiting good results can further be optimized for improved therapeutic profiles. However, investigations into the actions of neoflavonoids and tetrahydroquinolones, especially those related to the NFκB signaling pathway, aromatase inhibition, induction of quinone reductase 1 expression, and in vivo studies could provide new insights into the cancer chemopreventive ability of these molecules.
Molecular Bioprospection Department, Central Institute of Medicinal and Aromatic Plants-CSIR-CIMAP, Kukrail Picnic Spot Road, Lucknow 226015, India.
Suaib
S
Luqman
Abha
A
Meena
Pragya
P
Singh
Tamara P
TP
Kondratyuk
Laura E
LE
Marler
John M
JM
Pezzuto
Arvind S
AS
Negi
D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry* / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D016588:Anticarcinogenic Agents; D047072:Aromatase Inhibitors; D005419:Flavonoids; D016328:NF-kappa B; D015363:Quinolones; D014409:Tumor Necrosis Factor-alpha; D016660:NAD(P)H Dehydrogenase (Quinone)